Updated on 2024/02/22

写真a

 
UEMATSU Satoshi
 
Organization
Graduate School of Medicine Department of Basic Medical Science Professor
School of Medicine Department of Medical Science
Title
Professor
Affiliation
Institute of Medicine
Profile
May,1997-March,1999. Residency of Medical Doctor, Internal Medicine II at Hospital of Osaka City University Medical School (Prof. Hirotoshi Morii) April,2003-March,2004. Research Fellow (DC2) of Japan Society for the Promotion of Science (JSPS) April, 2004-October,2009. Assistant Professor, Department of Host Defense, Research Institute for Microbial Diseases, Osaka University (Prof. Shizuo Akira's lab) November,2009-May,2012. Associate Professor, Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University June,2012-present. Project Professor, Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo June, 2014-July, 2018. Professor, Department of Mucosal Immunology, Graduate School of Medicine and School of Medicine, Chiba University August, 2018-Present Professor, Department of Immunology and Genomics, Osaka City University Graduate School of Medicine and Faculty of Medicine

Position

  • Graduate School of Medicine Department of Basic Medical Science 

    Professor  2022.04 - Now

  • School of Medicine Department of Medical Science 

    Professor  2022.04 - Now

Degree

  • Doctor(Medicine) ( Osaka University )

Research Areas

  • Life Science / Immunology

  • Life Science / Bacteriology

  • Life Science / Infectious disease medicine

  • Life Science / Immunology

Research Interests

  • Innate immunity

  • mucosal immunology

  • meta genomics

  • vaccine

  • phage therapy

  • innate immunity

  • mucosal immunology

  • vaccine

  • meta genome

  • phage therapy

  • bacteriophage

Research subject summary

  • Although the intestinal immune system has evolved mechanisms that maintain immunological tolerance to food antigens and commensal organisms, it also recognizes invasive pathogens and induces appropriate protective immune responses to eliminate them. Innate immune cells such as dendritic cells and macrophages in intestine have unique features to induce Th17 cells, regulatory T cells and IgA-producing plasma cells, which play critical roles in intestine-specific immune responses.

    Our laboratory aims to clarify the whole mechanisms of intestinal immunity, which finely controls the balance between activation and tolerance by analyzing the function of each innate immune cell existed in intestinal mucosa.

    Since innate immunity initiates systemic immune responses, it is one of good targets for immune regulation. We will develop immunosuppression therapies for severe inflammatory diseases and allergic diseases, potent cancer immune therapies and effective vaccines by targeting on intestinal innate immune cells.

    Our laboratory belongs to Graduate School of Medicine, Chiba University and accepts graduate students of the master's course and doctor's course. We will train graduate students to acquire proficiency in analysis of mucosal immunity, to design experiments and to write articles. Finally, we will let graduate students decide the themes by themselves and carry them out. We try to develop professional researchers who can conduct researches independently.

    Our research goal is to control immune activation and tolerance at will. If you are interested in our researches, please come to and join our laboratory.

Professional Memberships

  • 日本免疫学会

      Domestic

  • The Japanese Society for Mucosal Immunology

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

Committee Memberships (off-campus)

  • 広報委員   日本免疫学会  

    2023.01 - Now 

  • 第20期科学研究費委員会   日本学術振興会  

    2019.01 - 2021.12 

Awards

  • 第46回多ケ谷勇記念ワクチン研究イスクラ奨励賞

    2021  

  • 第4回日本免疫学会研究奨励賞

    2009.12  

Job Career (off-campus)

  • 大阪公立大学大学院医学研究科・医学部   ゲノム免疫学   教授

    2022.04 - Now

  • 東京大学医科学研究所   ヒトゲノム解析センターメタゲノム医学分野   特任教授

    2020.04 - Now

  • Osaka City University Graduate School of Medicine   Immunology and Genomics   Professor

    2018.08 - 2022.03

  • 千葉大学   大学院医学研究院粘膜免疫学   教授

    2014.06 - 2018.09

  • Institute of Medical Science, The University of Tokyo   Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines   Project Professor,

    2012.06 - 2022.03

  • 大阪大学免疫学フロンティア研究センター(WPI)   自然免疫分野   特任准教授

    2009.11 - 2012.05

  • 大阪大学大阪大学微生物病研究所   自然免疫分野   助教

    2004.04 - 2009.10

  • 大阪市立大学医学部付属病院   第2内科   研修医

    1997.05 - 1999.03

▼display all

Education

  • Osaka University   Doctor's Course   Graduated/Completed

    2000.04 - 2004.03

  • Osaka City University     Graduated/Completed

    1991.04 - 1997.03

Papers

  • Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci. Reviewed

    Yokota C, Fujimoto K, Yamakawa N, Kono M, Miyaoka D, Shimohigoshi M, Uematsu M, Watanabe M, Kamei Y, Sugimoto A, Kawasaki N, Yabuno T, Okamura T, Kuroda E, Hamaguchi S, Sato S, Hotomi M, Akeda Y, Ishii KJ, Yasutomi Y, Sunami K, Uematsu S

    Inflammation and regeneration   43 ( 1 )   55   2023.11( ISSN:1880-9693

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s41232-023-00305-2

    PubMed

  • Prime-boost-type PspA3+2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci(タイトル和訳中) Reviewed

    Yokota Chieko, Fujimoto Kosuke, Yamakawa Natsuko, Kono Masamitsu, Miyaoka Daichi, Shimohigoshi Masaki, Uematsu Miho, Watanabe Miki, Kamei Yukari, Sugimoto Akira, Kawasaki Natsuko, Yabuno Takato, Okamura Tomotaka, Kuroda Eisuke, Hamaguchi Shigeto, Sato Shintaro, Hotomi Muneki, Akeda Yukihiro, Ishii Ken J., Yasutomi Yasuhiro, Sunami Kishiko, Uematsu Satoshi

    Inflammation and Regeneration   43   1 of 12 - 12 of 12   2023.11( ISSN:1880-9693

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    Publishing type:Research paper (scientific journal)  

  • ggkegg: analysis and visualization of KEGG data utilizing the grammar of graphics. Reviewed

    Sato N, Uematsu M, Fujimoto K, Uematsu S, Imoto S

    Bioinformatics (Oxford, England)   39 ( 10 )   2023.10( ISSN:1367-4803

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/bioinformatics/btad622

    PubMed

  • Zero-shot-capable identification of phage-host relationships with whole-genome sequence representation by contrastive learning. Reviewed

    Zhang YZ, Liu Y, Bai Z, Fujimoto K, Uematsu S, Imoto S

    Briefings in bioinformatics   24 ( 5 )   2023.09( ISSN:1467-5463

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/bib/bbad239

    PubMed

  • Orthognathic surgery with iliac bone grafting for an interpositional gap in a patient with type III hemifacial microsomia: A case report Reviewed

    Sugiyama M.

    JPRAS Open   37   55 - 62   2023.09

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jpra.2023.06.001

  • Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma. Reviewed

    Ayaka Takaori, Daisuke Hashimoto, Tsukasa Ikeura, Takashi Ito, Koh Nakamaru, Masataka Masuda, Shinji Nakayama, So Yamaki, Tomohisa Yamamoto, Kosuke Fujimoto, Yoshiyuki Matsuo, Shohei Akagawa, Mitsuaki Ishida, Kiyoshi Yamaguchi, Seiya Imoto, Kiichi Hirota, Satoshi Uematsu, Sohei Satoi, Mitsugu Sekimoto, Makoto Naganuma

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]   23 ( 4 )   367 - 376   2023.06( ISSN:1424-3903

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: /Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications. METHODS: Twenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences. RESULTS: Of the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and β-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01). CONCLUSIONS: The diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.

    DOI: 10.1016/j.pan.2023.04.001

    PubMed

  • The microsomal prostaglandin E synthase-1/PGE2 axis induces recovery from ischemia via recruitment of regulatory T cells. Reviewed

    Hideki Amano, Koji Eshima, Yoshiya Ito, Masaki Nakamura, Hidero Kitasato, Fumihiro Ogawa, Kanako Hosono, Kazuya Iwabuchi, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masataka Majima

    Cardiovascular research   119 ( 5 )   1218 - 1233   2023.05( ISSN:0008-6363

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    AIMS: Microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E2 (PGE2) induces angiogenesis through the prostaglandin E2 receptor (EP1-4). Among immune cells, regulatory T cells (Tregs), which inhibit immune responses, have been implicated in angiogenesis, and PGE2 is known to modulate function and differentiation of Tregs. We hypothesized that mPGES-1/PGE2-EP signaling could contribute to recovery from ischemic conditions by promoting the accumulation of Tregs. METHODS AND RESULTS: Wild-type (WT), mPGES-1-deficient (mPges-1-/-), and EP4 receptor-deficient (Ep4-/-) male mice 6-8 weeks old were used. Hindlimb ischemia was induced by femoral artery ligation. Recovery from ischemia was suppressed in mPges-1-/- mice and compared with WT mice. The number of accumulated forkhead box protein P3 (FoxP3)+ cells in ischemic muscle tissue was decreased in mPges-1-/- mice compared with that in WT mice. Expression levels of transforming growth factor-β (TGF-β) and stromal cell derived factor-1 (SDF-1) in ischemic tissue were also suppressed in mPges-1-/- mice. The number of accumulated FoxP3+ cells and blood flow recovery were suppressed when Tregs were depleted by injecting antibody against folate receptor 4 (FR4) in WT mice but not in mPges-1-/- mice. Recovery from ischemia was significantly suppressed in Ep4-/- mice compared with WT mice. Furthermore, mRNA levels of Foxp3 and Tgf-β were suppressed in Ep4-/- mice. Moreover, the numbers of accumulated FoxP3+ cells in ischemic tissue were diminished in Ep4-/- mice compared with Ep4+/+ mice. CONCLUSIONS: These findings suggested that mPGES-1/PGE2 induced neovascularization from ischemia via EP4 by promoting accumulation of Tregs. Highly selective EP4 agonists could be useful for treatment of peripheral artery disease (PAD). TRANSLATIONAL PERSPECTIVE: Although surgical treatment for PAD in patients improved, some patients with advanced disease have no other option for treatments other than amputation. In the present study, we revealed that endogenous mPGES-1/PGE2-EP4 signaling induced recovery from ischemia by promoting Tregs accumulation at the ischemic site. In addition, we showed that selective EP4 agonist, or transplantation of Tregs, induced recovery from ischemic conditions. These results indicate that the use of selective EP4 agonist, or cell therapy of Tregs, may be a potential treatment option for severe critical limb ischemia patients.

    DOI: 10.1093/cvr/cvac137

    PubMed

  • Survey of physicians’ attitudes toward computerized tomography imaging for pediatric head trauma Reviewed

    Shimokawa S.

    No To Hattatsu   55 ( 1 )   27 - 33   2023( ISSN:00290831

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    DOI: 10.11251/ojjscn.55.27

  • Characterization of the human gut virome in metabolic and autoimmune diseases. Reviewed

    Kosuke Fujimoto, Daichi Miyaoka, Satoshi Uematsu

    Inflammation and regeneration   42 ( 1 )   32 - 32   2022.11( ISSN:1880-9693

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    The intestinal microbiome is dominated by bacteria and plays a pivotal role in the occurrence and development of disease, including several metabolic and autoimmune disorders. While intestinal viral communities, primarily made up of bacteriophages, are also thought to play a role in disease pathogenesis in the gastrointestinal tract, they have received much less attention than intestinal bacteria. Thus, there is limited information about the relationship between bacteriophages and disease. This review explores a potential role for the intestinal viral microbiome in various metabolic and autoimmune diseases.

    DOI: 10.1186/s41232-022-00218-6

    PubMed

  • Identification of bacteriophage genome sequences with representation learning. Reviewed

    Zeheng Bai, Yao-Zhong Zhang, Satoru Miyano, Rui Yamaguchi, Kosuke Fujimoto, Satoshi Uematsu, Seiya Imoto

    Bioinformatics (Oxford, England)   38 ( 18 )   4264 - 4270   2022.09

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    MOTIVATION: Bacteriophages/phages are the viruses that infect and replicate within bacteria and archaea, and rich in human body. To investigate the relationship between phages and microbial communities, the identification of phages from metagenome sequences is the first step. Currently, there are two main methods for identifying phages: database-based (alignment-based) methods and alignment-free methods. Database-based methods typically use a large number of sequences as references; alignment-free methods usually learn the features of the sequences with machine learning and deep learning models. RESULTS: We propose INHERIT which uses a deep representation learning model to integrate both database-based and alignment-free methods, combining the strengths of both. Pre-training is used as an alternative way of acquiring knowledge representations from existing databases, while the BERT-style deep learning framework retains the advantage of alignment-free methods. We compare INHERIT with four existing methods on a third-party benchmark dataset. Our experiments show that INHERIT achieves a better performance with the F1-score of 0.9932. In addition, we find that pre-training two species separately helps the non-alignment deep learning model make more accurate predictions. AVAILABILITY AND IMPLEMENTATION: The codes of INHERIT are now available in: https://github.com/Celestial-Bai/INHERIT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

    DOI: 10.1093/bioinformatics/btac509

    PubMed

  • The Role of mPGES-1 in Promoting Granulation Tissue Angiogenesis Through Regulatory T-cell Accumulation. Reviewed

    Tetsuya Hyodo, Yoshiya Ito, Kanako Hosono, Satoshi Uematsu, Shizuo Akira, Masataka Majima, Akira Takeda, Hideki Amano

    In vivo (Athens, Greece)   36 ( 5 )   2061 - 2073   2022.09( ISSN:0258-851X

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND/AIM: Microsomal prostaglandin E synthase-1 (mPGES-1) is an enzyme, which catalyzes the final step of prostaglandin E2 (PGE2) synthesis. PGE2 in involved in wound-induced angiogenesis. Regulatory T cells (Tregs) regulate not only immune tolerance but also tissue repair and angiogenesis. We examined whether the mPGES-1/PGE2 axis contributes to wound-induced angiogenesis and granulation tissue formation through Treg accumulation. MATERIALS AND METHODS: The dorsal subcutaneous tissues of male mPGES-1-deficient (mPGES-1-/-) and C57BL/6 wild-type (WT) mice were implanted with polyurethane sponge disks. Angiogenesis was estimated by determining the wet weight of sponge tissues and the expression of proangiogenic factors including CD31, vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β) in granulation tissues. RESULTS: Angiogenesis was suppressed in mPGES-1-/- mice compared with WT mice, which was associated with attenuated forkhead box P3 (Foxp3) expression and Foxp3+ Treg accumulation. The number of cells double-positive for Foxp3/TGFβ and Foxp3/VEGF were lower in mPGES-1-/- mice than in WT mice. Neutralizing Tregs with antibodies (Abs) against CD25 or folate receptor 4 (FR4) inhibited the Foxp3+ Treg angiogenesis and accumulation in WT mice, but not in mPGES-1-/- mice. The topical application of PGE2 into the implanted sponge enhanced angiogenesis and accumulation of Tregs expressing TGFβ and VEGF in WT and mPGES-1-/- mice. CONCLUSION: Tregs producing TGFβ and VEGF accumulate in wounds and contribute to angiogenesis through mPGES-1-derived PGE2 mPGES-1 induction may control angiogenesis in skin wounds by recruiting Tregs.

    DOI: 10.21873/invivo.12932

    PubMed

  • Efficacy of Immune Checkpoint Inhibitor With or Without Chemotherapy for Nonsquamous NSCLC With Malignant Pleural Effusion: A Retrospective Multicenter Cohort Study Reviewed

    Kawachi H.

    JTO Clinical and Research Reports   3 ( 7 )   2022.07

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jtocrr.2022.100355

  • Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer. Reviewed

    Kentaro Masuhiro, Motohiro Tamiya, Kosuke Fujimoto, Shohei Koyama, Yujiro Naito, Akio Osa, Takashi Hirai, Hidekazu Suzuki, Norio Okamoto, Takayuki Shiroyama, Kazumi Nishino, Yuichi Adachi, Takuro Nii, Yumi Kinugasa-Katayama, Akiko Kajihara, Takayoshi Morita, Seiya Imoto, Satoshi Uematsu, Takuma Irie, Daisuke Okuzaki, Taiki Aoshi, Yoshito Takeda, Toru Kumagai, Tomonori Hirashima, Atsushi Kumanogoh

    JCI insight   7 ( 9 )   2022.05

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Bronchoalveolar lavage is commonly performed to assess inflammation and identify responsible pathogens in lung diseases, and its findings might be used to evaluate the immune profile of the lung tumor microenvironment (TME). To investigate whether bronchoalveolar lavage fluid (BALF) analysis can help identify non-small cell lung cancer (NSCLC) patients who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis were compared regarding therapeutic effect in 12 patients. Compared to ICI non-responders, responders showed significantly higher CXCL9 levels and a greater diversity of the lung microbiome profile in BALF, along with a greater frequency of the CD56+ subset in blood T cells, whereas no significant difference in PD-L1 expression was found in tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to anti-PD-1 antibody, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 might be associated with the lung TME microbiome, and their balance could contribute to nivolumab sensitivity in NSCLC patients. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.

    DOI: 10.1172/jci.insight.157915

    PubMed

  • Histologic transformation of epidermal growth factor receptor–mutated lung cancer Reviewed

    Fujimoto D.

    European Journal of Cancer   166   41 - 50   2022.05( ISSN:09598049

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ejca.2022.02.006

  • Galectin-3 promotes the adipogenic differentiation of PDGFRα+ cells and ectopic fat formation in regenerating muscle. Reviewed

    Naoki Takada, Masaki Takasugi, Yoshiki Nonaka, Tomonori Kamiya, Kazuaki Takemura, Junko Satoh, Shinji Ito, Kosuke Fujimoto, Satoshi Uematsu, Kayo Yoshida, Takashi Morita, Hiroaki Nakamura, Akiyoshi Uezumi, Naoko Ohtani

    Development (Cambridge, England)   149 ( 3 )   2022.02( ISSN:0950-1991

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.

    DOI: 10.1242/dev.199443

    PubMed

  • Interferon-α exerts proinflammatory properties in experimental radiation-induced esophagitis: Possible involvement of plasmacytoid dendritic cells. Reviewed

    Hiroyuki Kitamura, Tetsuya Tanigawa, Takuya Kuzumoto, Yuji Nadatani, Koji Otani, Shusei Fukunaga, Shuhei Hosomi, Fumio Tanaka, Noriko Kamata, Yasuaki Nagami, Koichi Taira, Satoshi Uematsu, Toshio Watanabe, Yasuhiro Fujiwara

    Life sciences   289   120215 - 120215   2022.01( ISSN:0024-3205

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    AIMS: Radiation-induced esophagitis, experienced during radiation therapy for lung cancer and head and neck cancer, is a major dose-limiting side effect of the treatment. This study aimed to elucidate the role of interferon-α (IFN-α) in radiation-induced esophagitis. MAIN METHODS: C57BL/6 mice were exposed to 10 and 25Gy of single thoracic irradiation. Esophageal mucosal damage and inflammatory reactions were assessed for 5 days after irradiation. KEY FINDINGS: Irradiation induced esophagitis, characterized by reduction in the thickness of epithelial layer, upregulation of proinflammatory cytokines and chemokines, infiltration of inflammatory cells into the esophageal mucosa, and apoptosis of epithelial cells. Irradiation upregulated the level of gene expression for IFN-α in the esophageal tissue, and the neutralizing antibody against IFN-α ameliorated radiation-induced esophageal mucosal damage, while administration of IFN-α receptor agonist (RO8191) had an inverse effect. Depletion of plasmacytoid dendritic cells (pDCs) by anti-CD317 antibody or pharmacological inactivation with bortezomib suppressed radiation-induced mucosal inflammation and damage, accompanied by decrease in IFN-α expression level. SIGNIFICANCE: These findings suggest that IFN-α and pDCs exert proinflammatory properties in the pathophysiology of radiation-induced esophagitis.

    DOI: 10.1016/j.lfs.2021.120215

    PubMed

  • 腸内細菌叢を標的とした新規治療法の開発

    植松 智

    日本マス・スクリーニング学会誌.   32(2)   168 - 168   2022

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  • 腸内細菌の異常と制御法.

    植松 智

    日本ペインクリニック学会誌.   29(4)   64 - 64   2022

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  • 生活習慣病と病原常在腸内細菌.

    植松 智

    臨床免疫・アレルギー科.   77(6)   684 - 689   2022

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  • いま知りたい!!ファージ療法は多剤耐性菌への切り札となるか 1 概論-ファージ療法の利点と課題.

    植松 智, 井元 清哉

    実験医学.   40(18)   2983 - 2985   2022

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  • 【自己免疫疾患 層別化する新時代へ 臨床検体のマルチオミクス解析、腸内細菌によって見えてきた免疫経路の全容】(第1章)精密医療を目指したマルチオミクス解析によるアプローチ メタゲノム解析からの層別化医療への展望.

    植松 智, 井元 清哉

    実験医学.   40(15)   2374 - 2379   2022

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  • Phage therapy for Clostridioides difficile infection. Reviewed

    Kosuke Fujimoto, Satoshi Uematsu

    Frontiers in immunology   13   1057892 - 1057892   2022

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Clostridioides difficile is endemic in the intestinal tract of healthy people. However, it is responsible for many healthcare-associated infections, such as nosocomial diarrhea following antibiotic treatment. Importantly, there have been cases of unsuccessful treatment and relapse related to the emergence of highly virulent strains of C. difficile and resistance to antimicrobial agents. Fecal microbiota transplantation (FMT) is considered an effective therapy for recurrent C. difficile infection. However, its safety is of concern because deaths caused by antibiotic-resistant bacterial infections after FMT were reported. Therefore, the development of effective C. difficile-specific treatments is urgently needed. In this review, we summarize the importance of phage therapy against C. difficile, and describe a novel next-generation phage therapy developed using metagenomic data.

    DOI: 10.3389/fimmu.2022.1057892

    PubMed

  • Dysbiosis関連疾患の新規治療法の開発.

    植松 智

    腸内細菌学雑誌   36(2)   66 - 67   2022

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  • Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice. Reviewed

    Satoshi Kosaka, Yuji Nadatani, Akira Higashimori, Koji Otani, Kosuke Fujimoto, Yuki Nagata, Masaki Ominami, Shusei Fukunaga, Shuhei Hosomi, Noriko Kamata, Fumio Tanaka, Yasuaki Nagami, Koichi Taira, Seiya Imoto, Satoshi Uematsu, Toshio Watanabe, Yasuhiro Fujiwara

    Microorganisms   9 ( 12 )   2021.12( ISSN:2076-2607

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.

    DOI: 10.3390/microorganisms9122563

    PubMed

  • Association between choriocapillaris flow deficit and choroidal neovascularization activity in eyes with myopic choroidal neovascularization Reviewed

    Uematsu S.

    Scientific Reports   11 ( 1 )   2021.12

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    DOI: 10.1038/s41598-021-01557-z

  • Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial Reviewed

    Yoshikazu Yuki, Masanori Nojima, Osamu Hosono, Hirotoshi Tanaka, Yasumasa Kimura, Takeshi Satoh, Seiya Imoto, Satoshi Uematsu, Shiho Kurokawa, Koji Kashima, Mio Mejima, Rika Nakahashi-Ouchida, Yohei Uchida, Takanori Marui, Noritada Yoshikawa, Fumitaka Nagamura, Kohtaro Fujihashi, Hiroshi Kiyono

    The Lancet Microbe   2 ( 9 )   e429 - e440   2021.09( ISSN:2666-5247

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    DOI: 10.1016/S2666-5247(20)30196-8

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  • Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation. Reviewed

    Kosuke Fujimoto, Yasumasa Kimura, Jessica R Allegretti, Mako Yamamoto, Yao-Zhong Zhang, Kotoe Katayama, Georg Tremmel, Yunosuke Kawaguchi, Masaki Shimohigoshi, Tetsuya Hayashi, Miho Uematsu, Kiyoshi Yamaguchi, Yoichi Furukawa, Yutaka Akiyama, Rui Yamaguchi, Sheila E Crowe, Peter B Ernst, Satoru Miyano, Hiroshi Kiyono, Seiya Imoto, Satoshi Uematsu

    Gastroenterology   160 ( 6 )   2089 - 2102.e12   2021.05( ISSN:0016-5085

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT. METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated. RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented. CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.

    DOI: 10.1053/j.gastro.2021.02.013

    PubMed

  • Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy. Reviewed

    Yoshihiro Takasato, Yosuke Kurashima, Masahiro Kiuchi, Kiyoshi Hirahara, Sayuri Murasaki, Fujimi Arai, Kumi Izawa, Ayako Kaitani, Kaoru Shimada, Yukari Saito, Shota Toyoshima, Miho Nakamura, Kumiko Fujisawa, Yoshimichi Okayama, Jun Kunisawa, Masato Kubo, Naoki Takemura, Satoshi Uematsu, Shizuo Akira, Jiro Kitaura, Takao Takahashi, Toshinori Nakayama, Hiroshi Kiyono

    Mucosal immunology   14 ( 3 )   640 - 651   2021.05( ISSN:1933-0219

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    Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.

    DOI: 10.1038/s41385-020-00358-3

    PubMed

  • Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation. Reviewed

    Fujimoto K, Kimura Y, Allegretti JR, Yamamoto M, Zhang YZ, Katayama K, Tremmel G, Kawaguchi Y, Shimohigoshi M, Hayashi T, Uematsu M, Yamaguchi K, Furukawa Y, Akiyama Y, Yamaguchi R, Crowe SE, Ernst PB, Miyano S, Kiyono H, Imoto S, Uematsu S

    Gastroenterology   2021.02( ISSN:0016-5085

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    DOI: 10.1053/j.gastro.2021.02.013

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  • Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice Reviewed

    Mukendi Jean Pierre Kambala, Nakamura Risa, Uematsu Satoshi, Hamano Shinjiro

    PARASITES & VECTORS   14 ( 1 )   70   2021.01( ISSN:1756-3305

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    DOI: 10.1186/s13071-020-04561-w

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  • Fecal Microbiome Composition in Healthy Adults in Ghana

    Parbie Prince Kofi, Mizutani Taketoshi, Ishizaka Aya, Kawana-Tachikawa Ai, Runtuwene Lucky Ronald, Seki Sayuri, Abana Christopher Zaab-Yen, Kushitor Dennis, Bonney Evelyn Yayra, Ofori Sampson Badu, Uematsu Satoshi, Imoto Seiya, Kimura Yasumasa, Kiyono Hiroshi, Ishikawa Koichi, Ampofo William Kwabena, Matano Tetsuro

    Japanese Journal of Infectious Diseases   74 ( 1 )   42 - 47   2021.01( ISSN:1344-6304

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    <p>Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by <i>Firmicutes</i> (<i>Faecalibacterium, Subdoligranulum</i>, and <i>Ruminococcaceae</i> UCG-014), <i>Proteobacteria</i> (<i>Escherichia-Shigella</i> and <i>Klebsiella</i>), and <i>Bacteroidetes</i> (<i>Prevotella</i> 9 and <i>Bacteroides</i>), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.</p>

    DOI: 10.7883/yoken.JJID.2020.469

    PubMed

    CiNii Article

  • Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice. Reviewed

    Jean Pierre Kambala Mukendi, Risa Nakamura, Satoshi Uematsu, Shinjiro Hamano

    Parasites & vectors   14 ( 1 )   70 - 70   2021.01

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    BACKGROUND: Schistosomes are trematode worms that dwell in their definitive host's blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice. METHODS: The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infected mice. RESULTS: Worms from IL-33-/- and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33-/- and WT mice differed only slightly. At 6 wpi, IL-33-/- mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33-/- and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues. CONCLUSIONS: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.

    DOI: 10.1186/s13071-020-04561-w

    PubMed

  • Fecal Microbiome Composition in Healthy Adults in Ghana(和訳中) Reviewed

    Parbie Prince Kofi, Mizutani Taketoshi, Ishizaka Aya, Kawana-Tachikawa Ai, Runtuwene Lucky Ronald, Seki Sayuri, Abana Christopher Zaab-Yen, Kushitor Dennis, Bonney Evelyn Yayra, Ofori Sampson Badu, Uematsu Satoshi, Imoto Seiya, Kimura Yasumasa, Kiyono Hiroshi, Ishikawa Koichi, Ampofo William Kwabena, Matano Tetsuro

    国立感染症研究所 Japanese Journal of Infectious Diseases   74 ( 1 )   42 - 47   2021.01( ISSN:1344-6304

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  • Fecal Microbiome Composition in Healthy Adults in Ghana Reviewed

    Parbie Prince Kofi, Mizutani Taketoshi, Ishizaka Aya, Kawana-Tachikawa Ai, Runtuwene Lucky Ronald, Seki Sayuri, Abana Christopher Zaab-Yen, Kushitor Dennis, Bonney Evelyn Yayra, Ofori Sampson Badu, Uematsu Satoshi, Imoto Seiya, Kimura Yasumasa, Kiyono Hiroshi, Ishikawa Koichi, Ampofo William Kwabena, Matano Tetsuro

    国立感染症研究所 Japanese Journal of Infectious Diseases 編集委員会 JAPANESE JOURNAL OF INFECTIOUS DISEASES   74 ( 1 )   42 - 47   2021.01( ISSN:1344-6304

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    <p>Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by <i>Firmicutes</i> (<i>Faecalibacterium, Subdoligranulum</i>, and <i>Ruminococcaceae</i> UCG-014), <i>Proteobacteria</i> (<i>Escherichia-Shigella</i> and <i>Klebsiella</i>), and <i>Bacteroidetes</i> (<i>Prevotella</i> 9 and <i>Bacteroides</i>), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.</p>

    DOI: 10.7883/yoken.JJID.2020.469

    PubMed

    CiNii Article

  • ガーナの健常成人における腸内細菌叢組成(Fecal Microbiome Composition in Healthy Adults in Ghana) Reviewed

    Parbie Prince Kofi, Mizutani Taketoshi, Ishizaka Aya, Kawana-Tachikawa Ai, Runtuwene Lucky Ronald, Seki Sayuri, Abana Christopher Zaab-Yen, Kushitor Dennis, Bonney Evelyn Yayra, Ofori Sampson Badu, Uematsu Satoshi, Imoto Seiya, Kimura Yasumasa, Kiyono Hiroshi, Ishikawa Koichi, Ampofo William Kwabena, Matano Tetsuro

    Japanese Journal of Infectious Diseases   74 ( 1 )   42 - 47   2021.01( ISSN:1344-6304

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    西アフリカのガーナにおける健常成人の腸内細菌叢の特性を評価した。横断研究には18歳以上の健康な55名を登録した。便を3回洗浄後遠心分離し、ペレットを再浮遊させ、セルストーナーで濾過してDNAを抽出した。16S rRNA遺伝子のV3-V4領域を、オーバーハングアダプター配列を含むプライマーで増幅し、アンプリコンのアダプターライゲーションを行った。次世代シーケンサーでシーケンス解析した。QIIME2を用いてシーケンスのクオリティフィルター、ノイズ除去、解析を行った。ガーナの健常成人の腸内細菌叢は、Firmicutes門(Faecalibacterium、Subdoligranulum、Ruminococcaceae UCG-014)、Proteobacteria門(Escherichia-Shigella、Klebsiella)、Bacteroidetes門(Prevotella 9、Bacteroides)が多数を占めていた。Ruminococcaceae UCG-014、Escherichia-Shigella、Klebsiellaはガーナ成人の最も豊富な7属に含まれたが、パプアニューギニアと米国のトップ20には入っていなかった。シャノンの多様度指数解析により、ガーナの成人の腸内細菌叢のα多様度は米国やパプアニューギニアの報告より有意に小さいことが示された。

  • Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana. Reviewed

    Prince Kofi Parbie, Taketoshi Mizutani, Aya Ishizaka, Ai Kawana-Tachikawa, Lucky Ronald Runtuwene, Sayuri Seki, Christopher Zaab-Yen Abana, Dennis Kushitor, Evelyn Yayra Bonney, Sampson Badu Ofori, Satoshi Uematsu, Seiya Imoto, Yasumasa Kimura, Hiroshi Kiyono, Koichi Ishikawa, William Kwabena Ampofo, Tetsuro Matano

    Frontiers in cellular and infection microbiology   11   646467 - 646467   2021

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.

    DOI: 10.3389/fcimb.2021.646467

    PubMed

  • Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy Reviewed

    Takasato Yoshihiro, Kurashima Yosuke, Kiuchi Masahiro, Hirahara Kiyoshi, Murasaki Sayuri, Arai Fujimi, Izawa Kumi, Kaitani Ayako, Shimada Kaoru, Saito Yukari, Toyoshima Shota, Nakamura Miho, Fujisawa Kumiko, Okayama Yoshimichi, Kunisawa Jun, Kubo Masato, Takemura Naoki, Uematsu Satoshi, Akira Shizuo, Kitaura Jiro, Takahashi Takao, Nakayama Toshinori, Kiyono Hiroshi

    MUCOSAL IMMUNOLOGY   2020.12( ISSN:1933-0219

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    DOI: 10.1038/s41385-020-00358-3

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  • Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota Reviewed

    Ishida Sachiko, Kato Kumiko, Tanaka Masami, Odamaki Toshitaka, Kubo Ryuichi, Mitsuyama Eri, Xiao Jin-zhong, Yamaguchi Rui, Uematsu Satoshi, Imoto Seiya, Miyano Satoru

    COMMUNICATIONS BIOLOGY   3 ( 1 )   686   2020.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s42003-020-01416-z

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  • Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota. Reviewed

    Sachiko Ishida, Kumiko Kato, Masami Tanaka, Toshitaka Odamaki, Ryuichi Kubo, Eri Mitsuyama, Jin-Zhong Xiao, Rui Yamaguchi, Satoshi Uematsu, Seiya Imoto, Satoru Miyano

    Communications biology   3 ( 1 )   686 - 686   2020.11

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Numerous host extrinsic and intrinsic factors affect the gut microbiota composition, but their cumulative effects do not sufficiently explain the variation in the microbiota, suggesting contributions of missing factors. The Japanese population possesses homogeneous genetic features suitable for genome-wide association study (GWAS). Here, we performed GWASs for human gut microbiota using 1068 healthy Japanese adults. To precisely evaluate genetic effects, we corrected for the impacts of numerous host extrinsic and demographic factors by introducing them as covariates, enabling us to discover five loci significantly associated with microbiome diversity measures: HS3ST4, C2CD2, 2p16.1, 10p15.1, and 18q12.2. Nevertheless, these five variants explain only a small fraction of the variation in the gut microbiota. We subsequently investigated the heritability of each of the 21 core genera and found that the abundances of six genera are heritable. We propose that the gut microbiota composition is affected by a highly polygenic architecture rather than several strongly associated variants in the Japanese population.

    DOI: 10.1038/s42003-020-01416-z

    PubMed

  • Alcohol abrogates human norovirus infectivity in a pH-dependent manner Reviewed

    Sato Shintaro, Matsumoto Naomi, Hisaie Kota, Uematsu Satoshi

    SCIENTIFIC REPORTS   10 ( 1 )   15878   2020.09( ISSN:2045-2322

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    DOI: 10.1038/s41598-020-72609-z

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  • Alcohol abrogates human norovirus infectivity in a pH-dependent manner. Reviewed

    Shintaro Sato, Naomi Matsumoto, Kota Hisaie, Satoshi Uematsu

    Scientific reports   10 ( 1 )   15878 - 15878   2020.09

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Alcohol-based disinfectants are widely used for the sanitization of microorganisms, especially those that cause infectious diseases, including viruses. However, since the germicidal mechanism of alcohol is lipolysis, alcohol-based disinfectants appear to have a minimal effect on non-enveloped viruses, such as noroviruses. Because there is no cultivation method for human norovirus (HuNoV) in vitro, murine norovirus and feline calicivirus have been used as surrogates for HuNoV to analyze the efficacy of disinfectant regents. Therefore, whether these disinfectants and their conditions are effective against HuNoVs remain unknown. In this study, we report that ethanol or isopropanol alone can sufficiently suppress GII.4 genotype HuNoV replication in human iPSC-derived intestinal epithelial cells. Additionally, pH adjustments and salting-out may contribute toward the virucidal effect of alcohol against other HuNoV genotypes and cancel the impediment of organic substance contamination, respectively. Therefore, similar to sodium hypochlorite, alcohol-based disinfectants containing electrolytes can be used for HuNoV inactivation.

    DOI: 10.1038/s41598-020-72609-z

    PubMed

  • Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts Reviewed

    Fujimoto Kosuke, Kimura Yasumasa, Shimohigoshi Masaki, Satoh Takeshi, Sato Shintaro, Tremmel Georg, Uematsu Miho, Kawaguchi Yunosuke, Usui Yuki, Nakano Yoshiko, Hayashi Tetsuya, Kashima Koji, Yuki Yoshikazu, Yamaguchi Kiyoshi, Furukawa Yoichi, Kakuta Masanori, Akiyama Yutaka, Yamaguchi Rui, Crowe Sheila E., Ernst Peter B., Miyano Satoru, Kiyono Hiroshi, Imoto Seiya, Uematsu Satoshi

    CELL HOST & MICROBE   28 ( 3 )   380 - +   2020.09( ISSN:1931-3128

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    DOI: 10.1016/j.chom.2020.06.005

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  • Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts. Reviewed

    Kosuke Fujimoto, Yasumasa Kimura, Masaki Shimohigoshi, Takeshi Satoh, Shintaro Sato, Georg Tremmel, Miho Uematsu, Yunosuke Kawaguchi, Yuki Usui, Yoshiko Nakano, Tetsuya Hayashi, Koji Kashima, Yoshikazu Yuki, Kiyoshi Yamaguchi, Yoichi Furukawa, Masanori Kakuta, Yutaka Akiyama, Rui Yamaguchi, Sheila E Crowe, Peter B Ernst, Satoru Miyano, Hiroshi Kiyono, Seiya Imoto, Satoshi Uematsu

    Cell host & microbe   28 ( 3 )   380 - 389.e9   2020.09( ISSN:1931-3128

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    The application of bacteriophages (phages) is proposed as a highly specific therapy for intestinal pathobiont elimination. However, the infectious associations between phages and bacteria in the human intestine, which is essential information for the development of phage therapies, have yet to be fully elucidated. Here, we report the intestinal viral microbiomes (viromes), together with bacterial microbiomes (bacteriomes), in 101 healthy Japanese individuals. Based on the genomic sequences of bacteriomes and viromes from the same fecal samples, the host bacteria-phage associations are illustrated for both temperate and virulent phages. To verify the usefulness of the comprehensive host bacteria-phage information, we screened Clostridioides difficile-specific phages and identified antibacterial enzymes whose activity is confirmed both in vitro and in vivo. These comprehensive metagenome analyses reveal not only host bacteria-phage associations in the human intestine but also provide vital information for the development of phage therapies against intestinal pathobionts.

    DOI: 10.1016/j.chom.2020.06.005

    PubMed

  • Development of prime-boost-type next-generation mucosal vaccines. Reviewed

    Kosuke Fujimoto, Satoshi Uematsu

    International immunology   32 ( 9 )   597 - 603   2020.09( ISSN:0953-8178

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    Our bodies are constantly exposed to a wide variety of pathogenic micro-organisms through mucosal sites. Therefore, effective vaccines that can protect at the mucosa are vital; however, only a few clinically established mucosal vaccines are available. Although conventional injectable vaccines can induce antigen-specific serum immunoglobulin G (IgG) and prevent severe infection, it is difficult to efficiently inhibit the invasion of pathogens at mucosal surfaces because of the inadequate ability to induce antigen-specific IgA. Recently, we have developed a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides and reported its application. Unlike other conventional injectable vaccines, this immunization contributes to the induction of antigen-specific mucosal and systemic immune responses. Even if antigen-specific IgA at the mucosa disappears, this immunization can induce high-titer IgA after boosting with a small amount of antigen on the target mucosal surface. Indeed, vaccination with Streptococcus pneumoniae antigen effectively prevented lung infection induced by this bacterium. In addition, vaccination with Clostridium ramosum, which is a representative pathobiont associated with obesity and diabetes in humans, reduced obesity in mice colonized with this microorganism. This immunization approach might be an effective treatment for intestinal bacteria-mediated diseases that have been difficult to regulate so far, as well as common infectious diseases.

    DOI: 10.1093/intimm/dxz085

    PubMed

  • Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice Reviewed

    Takashima Shingo, Tanaka Fumio, Kawaguchi Yunoske, Usui Yuki, Fujimoto Kosuke, Nadatani Yuji, Otani Koji, Hosomi Shuhei, Nagami Yasuaki, Kamata Noriko, Taira Koichi, Tanigawa Tetsuya, Watanabe Toshio, Imoto Seiya, Uematsu Satoshi, Fujiwara Yasuhiro

    NEUROGASTROENTEROLOGY AND MOTILITY   32 ( 7 )   e13841   2020.07( ISSN:1350-1925

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    DOI: 10.1111/nmo.13841

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  • Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice. Reviewed

    Shingo Takashima, Fumio Tanaka, Yunosuke Kawaguchi, Yuki Usui, Kosuke Fujimoto, Yuji Nadatani, Koji Otani, Shuhei Hosomi, Yasuaki Nagami, Noriko Kamata, Koichi Taira, Tetsuya Tanigawa, Toshio Watanabe, Seiya Imoto, Satoshi Uematsu, Yasuhiro Fujiwara

    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society   32 ( 7 )   e13841   2020.07( ISSN:1350-1925

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions. METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40 mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2. KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis. CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.

    DOI: 10.1111/nmo.13841

    PubMed

  • Vaccine therapy for dysbiosis-related diseases Reviewed

    Fujimoto Kosuke, Uematsu Satoshi

    WORLD JOURNAL OF GASTROENTEROLOGY   26 ( 21 )   2758 - 2767   2020.06( ISSN:1007-9327

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    DOI: 10.3748/wjg.v26.i21.2758

    PubMed

  • Vaccine therapy for dysbiosis-related diseases. Reviewed

    Kosuke Fujimoto, Satoshi Uematsu

    World journal of gastroenterology   26 ( 21 )   2758 - 2767   2020.06( ISSN:1007-9327

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    Progress in genomic analysis has resulted in the proposal that the intestinal microbiota is a crucial environmental factor in the development of multifactorial diseases, such as obesity, diabetes, rheumatoid arthritis, and inflammatory bowel diseases represented by Crohn's disease and ulcerative colitis. Dysregulated gut microbiome contributes to the pathogenesis of such disorders; however, there are few effective treatments for controlling only disease-mediating bacteria. Here, we review current knowledge about the intestinal microbiome in health and disease, and discuss a regulatory strategy using a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides, which we have recently developed. Unlike other conventional injectable immunizations, our vaccine contributes to the induction of antigen-specific systemic and mucosal immunity. This vaccine strategy can prevent infectious diseases such as Streptococcus pneumoniae infection, and control metabolic symptoms mediated by intestinal bacteria (e.g. Clostridium ramosum) by induction of high titers of antigen-specific IgA at target mucosal sites. In the future, our vaccination approach could be an effective therapy for common infectious diseases and dysbiosis-related disorders that have been difficult to control so far.

    DOI: 10.3748/wjg.v26.i21.2758

    PubMed

  • Microsomal prostaglandin E synthase-1 promotes lung metastasis via SDF-1/CXCR4-mediated recruitment of CD11b+Gr1+MDSCs from bone marrow. Reviewed

    Ryo Takahashi, Hideki Amano, Yoshiya Ito, Koji Eshima, Takefumi Satoh, Masatsugu Iwamura, Masaki Nakamura, Hidero Kitasato, Satoshi Uematsu, Joan Raouf, Per-Johan Jakobsson, Shizuo Akira, Masataka Majima

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   121   109581 - 109581   2020.01( ISSN:0753-3322

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    BACKGROUND: Accumulation of myeloid-derived suppressor cells (MDSCs) to tumors is related to cancer prognosis. We investigated the contribution of host stromal microsomal prostaglandin E synthase-1 (mPGES-1) to the accumulation of MDSCs in metastasized lungs of prostate cancer in mice. MATERIAL AND METHODS: Eight-week-old male C57Bl/6 wild type (WT) mice and mPGES-1 knock out mice (mPGES-1KO) were injected with RM9 murine prostate cancer cell line (5 × 106 cells/mL). Lung metastasis was evaluated by the number of colonies, the weight of the lung, and the number of MDSCs (CD11b+Gr1+ cells) in the lung. RESULTS: Intravenous injections of RM9, a murine prostate cancer cell line to WT mice revealed that lung metastasis and accumulation of MDCSs were suppressed with treatments with a Gr1 antibody, a COX-2 inhibitor, and an mPGES-1 inhibitor. Lung metastasis and accumulation of CD11b+Gr1+MDSCs were suppressed in mPGES-1KO mice. The mRNA level of stromal cell-derived factor-1 (SDF-1) in the lung and the number of accumulated SDF-1-expressing CD11b+Gr1+ MDSCs were elevated at an early stage in lung metastasis of C-X-C chemokine receptor type 4 (CXCR4)-expressing RM9 in an mPGES-1-dependent manner. The number of CXCR4-expressing CD11b+Gr1+MDSCs in WT mice was higher than that in mPGES-1KO mice. RM9 lung metastasis and accumulation of CD11b+Gr1+MDSCs were suppressed by CXCR4 antibody in WT mice but not in mPGES-1KO. WT mice transplanted with mPGES-1 KO bone marrow (BM) showed a significant reduction in lung metastasis and accumulation of CD11b+Gr1+MDSCs. CONCLUSION: These results suggest that mPGES-1 enhances tumor metastasis by inducing accumulation of BM-derived MDSCs. Selective mPGES-1 inhibitors might, therefore, represent valuable therapeutic tools for the suppression of tumor metastasis.

    DOI: 10.1016/j.biopha.2019.109581

    PubMed

  • Development of prime-boost-type next-generation mucosal vaccines. Reviewed

    Fujimoto K, Uematsu S

    International immunology   2019.12( ISSN:0953-8178

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    DOI: 10.1093/intimm/dxz085

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  • Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases. Reviewed

    Kosuke Fujimoto, Yunosuke Kawaguchi, Masaki Shimohigoshi, Yoshiyuki Gotoh, Yoshiko Nakano, Yuki Usui, Tetsuya Hayashi, Yasumasa Kimura, Miho Uematsu, Takuya Yamamoto, Yukihiro Akeda, Joon Haeng Rhee, Yoshikazu Yuki, Ken J Ishii, Sheila E Crowe, Peter B Ernst, Hiroshi Kiyono, Satoshi Uematsu

    Gastroenterology   157 ( 6 )   1530 - 1543.e4   2019.12( ISSN:0016-5085

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.

    DOI: 10.1053/j.gastro.2019.08.021

    PubMed

  • High-fat diet-mediated dysbiosis exacerbates NSAID-induced small intestinal damage through the induction of interleukin-17A. Reviewed

    Sugimura N, Otani K, Watanabe T, Nakatsu G, Shimada S, Fujimoto K, Nadatani Y, Hosomi S, Tanaka F, Kamata N, Taira K, Nagami Y, Tanigawa T, Uematsu S, Fujiwara Y

    Scientific reports   9 ( 1 )   16796   2019.11

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    DOI: 10.1038/s41598-019-52980-2

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  • High-fat diet-mediated dysbiosis exacerbates NSAID-induced small intestinal damage through the induction of interleukin-17A. Reviewed

    Naoki Sugimura, Koji Otani, Toshio Watanabe, Geicho Nakatsu, Sunao Shimada, Kosuke Fujimoto, Yuji Nadatani, Shuhei Hosomi, Fumio Tanaka, Noriko Kamata, Koichi Taira, Yasuaki Nagami, Tetsuya Tanigawa, Satoshi Uematsu, Yasuhiro Fujiwara

    Scientific reports   9 ( 1 )   16796 - 16796   2019.11( ISSN:2045-2322

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    Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage in the small intestine in a bacteria-dependent manner. As high-fat diet (HFD) is a potent inducer of gut dysbiosis, we investigated the effects of HFD on bacterial flora in the small intestine and NSAID-induced enteropathy. 16S rRNA gene analysis revealed that the population of Bifidobacterium spp. significantly decreased by fold change of individual operational taxonomic units in the small intestine of mice fed HFD for 8 weeks. HFD increased intestinal permeability, as indicated by fluorescein isothiocyanate-dextran absorption and serum lipopolysaccharide levels, accompanied by a decrease in the protein expressions of ZO-1 and occludin and elevated mRNA expression of interleukin (IL)-17A in the small intestine. HFD-fed mice exhibited increased susceptibility to indomethacin-induced damage in the small intestine; this phenotype was observed in normal diet-fed mice that received small intestinal microbiota from HFD-fed mice. Administration of neutralizing antibodies against IL-17A to HFD-fed mice reduced intestinal permeability and prevented exacerbation of indomethacin-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation through the induction of IL-17A and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.

    DOI: 10.1038/s41598-019-52980-2

    PubMed

  • Microsomal prostaglandin E synthase-1 promotes lung metastasis via SDF-1/CXCR4-mediated recruitment of CD11b<sup>+</sup>Gr1<sup>+</sup>MDSCs from bone marrow. Reviewed

    Takahashi R, Amano H, Ito Y, Eshima K, Satoh T, Iwamura M, Nakamura M, Kitasato H, Uematsu S, Raouf J, Jakobsson PJ, Akira S, Majima M

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   121   109581   2019.11( ISSN:0753-3322

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    DOI: 10.1016/j.biopha.2019.109581

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  • Diet-Induced Obese Mice and Leptin-Deficient Lep(ob/ob) Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms Reviewed

    Lee Eunyoung, Miedzybrodzka Emily L., Zhang Xilin, Hatano Ryo, Miyamoto Junki, Kimura Ikuo, Fujimoto Kosuke, Uematsu Satoshi, Rodriguez-Cuenca Sergio, Vidal-Puig Antonio, Gribble Fiona M., Reimann Frank, Miki Takashi

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   20 ( 18 )   2019.09

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    DOI: 10.3390/ijms20184448

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  • Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases. Reviewed

    Fujimoto K, Kawaguchi Y, Shimohigoshi M, Gotoh Y, Nakano Y, Usui Y, Hayashi T, Kimura Y, Uematsu M, Yamamoto T, Akeda Y, Rhee JH, Yuki Y, Ishii KJ, Crowe SE, Ernst PB, Kiyono H, Uematsu S

    Gastroenterology   2019.08( ISSN:0016-5085

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    DOI: 10.1053/j.gastro.2019.08.021

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  • Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson's disease. Reviewed

    Ikeda-Matsuo Y, Miyata H, Mizoguchi T, Ohama E, Naito Y, Uematsu S, Akira S, Sasaki Y, Tanabe M

    Neurobiology of disease   124   81 - 92   2019.04( ISSN:0969-9961

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    DOI: 10.1016/j.nbd.2018.11.004

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  • Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson's disease. Reviewed

    Ikeda-Matsuo Y, Miyata H, Mizoguchi T, Ohama E, Naito Y, Uematsu S, Akira S, Sasaki Y, Tanabe M

    Neurobiology of disease   124   81 - 92   2019.04( ISSN:0969-9961

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    Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Although increased production of prostaglandin E2 (PGE2) has been implicated in tissue damage in several pathological settings, the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE2 synthesis, in dopaminergic neurodegeneration remains unclear. Here we show that mPGES-1 is up-regulated in the dopaminergic neurons of the substantia nigra of postmortem brain tissue from PD patients and in neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. The expression of mPGES-1 was also up-regulated in cultured dopaminergic neurons stimulated with 6-OHDA. The genetic deletion of mPGES-1 not only abolished 6-OHDA-induced PGE2 production but also inhibited 6-OHDA-induced dopaminergic neurodegeneration both in vitro and in vivo. Nigrostriatal projections, striatal dopamine content, and neurological functions were significantly impaired by 6-OHDA administration in wild-type (WT) mice, but not in mPGES-1 knockout (KO) mice. Furthermore, in cultured primary mesencephalic neurons, addition of PGE2 to compensate for the deficiency of 6-OHDA-induced PGE2 production in mPGES-1 KO neurons recovered 6-OHDA toxicity to almost the same extent as that seen in WT neurons. These results suggest that induction of mPGES-1 enhances 6-OHDA-induced dopaminergic neuronal death through excessive PGE2 production. Thus, mPGES-1 may be a valuable therapeutic target for treatment of PD.

    DOI: 10.1016/j.nbd.2018.11.004

    PubMed

  • Diet-Induced Obese Mice and Leptin-deficient Lepob/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms Reviewed

    • Lee EY, Miedzbrodzka E, Zhang X, Hatano R, Miyamoto J, Kimura I, Fujimoto K, Uematsu S, Rodriguez-Cuenca S, Vidal-Puig A, Gribble FM, Reimann F, Miki T

    Int J Mol Sci   20   4448   2019

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  • Induction of mPGES-1 in dopaminergic neurons contributes to neurodegeneration in Parkinson's disease Reviewed

    Ikeda-Matsuo Yuri, Miyata Hajime, Mizoguchi Tomoko, Naito Yasuhito, Uematsu Satoshi, Akira Shizuo, Sasaki Yasuharu, Tanabe Mitsuo

    Japanese Pharmacological Society, Proceedings for Annual Meeting of The Japanese Pharmacological Society   92 ( 0 )   1 - O-16   2019

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    <p>Although increased production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) has been implicated in tissue damage in several pathological settings, the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE<sub>2</sub> synthesis, in dopaminergic neurodegeneration remains unclear. Here we show that mPGES-1 is up-regulated in the dopaminergic neurons of the substantia nigra of postmortem brain tissue from PD patients and in 6-hydroxydopamine (6-OHDA)-induced PD mice. The expression of mPGES-1 was also up-regulated in cultured dopaminergic neurons stimulated with 6-OHDA. The genetic deletion of mPGES-1 not only abolished 6-OHDA-induced PGE<sub>2</sub> production but also attenuated 6-OHDA-induced dopaminergic neurodegeneration both<i> in vitro</i> and<i> in vivo</i>, while it did not affect the productions of PGI<sub>2</sub>, PGD<sub>2</sub> and TXA<sub>2.</sub> Nigrostriatal projections, striatal dopamine content, and neurological functions were significantly impaired by 6-OHDA administration in wild-type mice, but not in mPGES-1 knockout mice. These results suggest that induction of mPGES-1 in dopaminergic neurons enhances 6-OHDA-induced dopaminergic neurodegeneration through excessive PGE<sub>2</sub> production. Thus, mPGES-1 may be a valuable therapeutic target for treatment of PD</p>

    DOI: 10.1254/jpssuppl.92.0_1-O-16

    CiNii Article

  • 腸内細菌叢(腸内フローラ)とは Reviewed

    植松 智

    糖尿病ケア   17(1)   9 - 10   2019

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  • 腸内細菌が乱れる原因と体に及ぼす影響 Reviewed

    植松 智

    糖尿病ケア   17(1)   11 - 13   2019

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  • 放射線腸障害に及ぼす好酸球の役割

    藤本 康介, 植松 智

    アレルギーの臨床   Vol.39(14)   13 - 16   2019

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  • Induction of mPGES-1 in dopaminergic neurons contributes to neurodegeneration in Parkinson's disease

    Ikeda-Matsuo Yuri, Miyata Hajime, Mizoguchi Tomoko, Naito Yasuhito, Uematsu Satoshi, Akira Shizuo, Sasaki Yasuharu, Tanabe Mitsuo

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   92 ( 0 )   1-O-16 - O-16   2019

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    <p>Although increased production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) has been implicated in tissue damage in several pathological settings, the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE<sub>2</sub> synthesis, in dopaminergic neurodegeneration remains unclear. Here we show that mPGES-1 is up-regulated in the dopaminergic neurons of the substantia nigra of postmortem brain tissue from PD patients and in 6-hydroxydopamine (6-OHDA)-induced PD mice. The expression of mPGES-1 was also up-regulated in cultured dopaminergic neurons stimulated with 6-OHDA. The genetic deletion of mPGES-1 not only abolished 6-OHDA-induced PGE<sub>2</sub> production but also attenuated 6-OHDA-induced dopaminergic neurodegeneration both<i> in vitro</i> and<i> in vivo</i>, while it did not affect the productions of PGI<sub>2</sub>, PGD<sub>2</sub> and TXA<sub>2.</sub> Nigrostriatal projections, striatal dopamine content, and neurological functions were significantly impaired by 6-OHDA administration in wild-type mice, but not in mPGES-1 knockout mice. These results suggest that induction of mPGES-1 in dopaminergic neurons enhances 6-OHDA-induced dopaminergic neurodegeneration through excessive PGE<sub>2</sub> production. Thus, mPGES-1 may be a valuable therapeutic target for treatment of PD</p>

    DOI: 10.1254/jpssuppl.92.0_1-o-16

    CiNii Article

  • Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway. Reviewed

    Lee EY, Zhang X, Miyamoto J, Kimura I, Taknaka T, Furusawa K, Jomori T, Fujimoto K, Uematsu S, Miki T

    The Journal of endocrinology   239 ( 3 )   267 - 276   2018.12( ISSN:0022-0795

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    DOI: 10.1530/JOE-18-0241

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  • Virome analysis in intestine Reviewed

    Uematsu Satoshi

    CANCER SCIENCE   109   348 - 348   2018.12( ISSN:1349-7006

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  • Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes. Reviewed

    Komine O, Yamashita H, Fujimori-Tonou N, Koike M, Jin S, Moriwaki Y, Endo F, Watanabe S, Uematsu S, Akira S, Uchiyama Y, Takahashi R, Misawa H, Yamanaka K

    Cell death and differentiation   25 ( 12 )   2130 - 2146   2018.12( ISSN:1350-9047

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    DOI: 10.1038/s41418-018-0098-3

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  • Intestinal CD103(+) CD11b(+) cDC2 Conventional Dendritic Cells Are Required for Primary CD4(+) T and B Cell Responses to Soluble Flagellin Reviewed

    Flores-Langarica Adriana, Cook Charlotte, Luda Katarzyna Muller, Persson Emma K., Marshall Jennifer L., Beristain-Covarrubias Nonantzin, Yam-Puc Juan Carlos, Dahlgren Madelene, Persson Jenny J., Uematsu Satoshi, Akira Shizuo, Henderson Ian R., Lindbom Bengt Johansson, Agace William, Cunningham Adam F.

    FRONTIERS IN IMMUNOLOGY   9   2409   2018.10( ISSN:1664-3224

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    DOI: 10.3389/fimmu.2018.02409

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  • DUSP10 constrains innate IL-33-mediated cytokine production in ST2<sup>hi</sup> memory-type pathogenic Th2 cells. Reviewed

    Yamamoto T, Endo Y, Onodera A, Hirahara K, Asou HK, Nakajima T, Kanno T, Ouchi Y, Uematsu S, Nishimasu H, Nureki O, Tumes DJ, Shimojo N, Nakayama T

    Nature communications   9 ( 1 )   4231   2018.10

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    DOI: 10.1038/s41467-018-06468-8

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  • Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice. Reviewed

    Nishizawa N, Ito Y, Eshima K, Ohkubo H, Kojo K, Inoue T, Raouf J, Jakobsson PJ, Uematsu S, Akira S, Narumiya S, Watanabe M, Majima M

    Journal of hepatology   69 ( 1 )   110 - 120   2018.07( ISSN:0168-8278

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    DOI: 10.1016/j.jhep.2018.02.009

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  • Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice(和訳中) Reviewed

    Usui Yuki, Kimura Yasumasa, Satoh Takeshi, Takemura Naoki, Ouchi Yasuo, Ohmiya Hiroko, Kobayashi Kyosuke, Suzuki Hiromi, Koyama Satomi, Hagiwara Satoko, Tanaka Hirotoshi, Imoto Seiya, Eberl Gerard, Asami Yukio, Fujimoto Kosuke, Uematsu Satoshi

    Oxford University Press International Immunology   30 ( 7 )   319 - 331   2018.07( ISSN:0953-8178

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  • Lactobacillus delbrueckii subsp. bulgaricus 2038とStreptococcus thermophilus 1131で発酵させたヨーグルトの長期摂取がマウスに及ぼす影響(Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice) Reviewed

    Usui Yuki, Kimura Yasumasa, Satoh Takeshi, Takemura Naoki, Ouchi Yasuo, Ohmiya Hiroko, Kobayashi Kyosuke, Suzuki Hiromi, Koyama Satomi, Hagiwara Satoko, Tanaka Hirotoshi, Imoto Seiya, Eberl Gerard, Asami Yukio, Fujimoto Kosuke, Uematsu Satoshi

    International Immunology   30 ( 7 )   319 - 331   2018.07( ISSN:0953-8178

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    マウスにLB81ヨーグルトを長期摂取させ、生存率、体重、糞中マイクロバイオーム、糞中代謝物、種々の器官における遺伝子発現への影響を評価した。マウスに正常食またはLB81ヨーグルトを含む食餌を与え、生存率と体重変化をモニタリングした。糞便検体を採取し、細菌DNAを抽出して16S rRNA遺伝子解析を行い、メタボローム解析を実施した。空腸、回腸、遠位結腸、肝臓、脾臓組織を採取し、マイクロアレイ解析を行った。LB81ヨーグルトの長期摂取はFirmicutesに対するBacteroidetesの比率を増加させ、細菌ファミリーS24-7の存在量を上昇させた。長期LB81ヨーグルト摂取によってプロピオン酸およびブタン酸に関連する腸内代謝経路が変化した。防御応答に関連する多くの生理学的機能に影響を与えた。抗菌ペプチド、タイト結合、接着接合、粘液関連腸内バリア機能に関連する種々の遺伝子プロファイルが大幅に変化した。LB81ヨーグルトの長期摂取は、腸内マイクロバイオームとその代謝物を調節することで、腸内バリア機能などの全身恒常性を維持する可能性が示された。

  • Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice. Reviewed

    Usui Y, Kimura Y, Satoh T, Takemura N, Ouchi Y, Ohmiya H, Kobayashi K, Suzuki H, Koyama S, Hagiwara S, Tanaka H, Imoto S, Eberl G, Asami Y, Fujimoto K, Uematsu S

    International immunology   30 ( 7 )   319 - 331   2018.06( ISSN:0953-8178

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    DOI: 10.1093/intimm/dxy035

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  • Generation of tumor antigen-specific murine CD8+ T cells with enhanced anti-tumor activity via highly efficient CRISPR/Cas9 genome editing. Reviewed

    Ouchi Y, Patil A, Tamura Y, Nishimasu H, Negishi A, Paul SK, Takemura N, Satoh T, Kimura Y, Kurachi M, Nureki O, Nakai K, Kiyono H, Uematsu S

    International immunology   30 ( 4 )   141 - 154   2018.04( ISSN:0953-8178

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    DOI: 10.1093/intimm/dxy006

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  • Generation of tumor antigen-specific murine CD8+ T cells with enhanced anti-tumor activity via highly efficient CRISPR/Cas9 genome editing(和訳中) Reviewed

    Ouchi Yasuo, Patil Ashwini, Tamura Yusuke, Nishimasu Hiroshi, Negishi Aina, Paul Sudip Kumar, Takemura Naoki, Satoh Takeshi, Kimura Yasumasa, Kurachi Makoto, Nureki Osamu, Nakai Kenta, Kiyono Hiroshi, Uematsu Satoshi

    Oxford University Press International Immunology   30 ( 4 )   141 - 154   2018.04( ISSN:0953-8178

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  • 高効率なCRISPR/Cas9ゲノム編集によって抗腫瘍活性が増強された腫瘍抗原特異的マウスCD8+T細胞の作製(Generation of tumor antigen-specific murine CD8+ T cells with enhanced anti-tumor activity via highly efficient CRISPR/Cas9 genome editing) Reviewed

    Ouchi Yasuo, Patil Ashwini, Tamura Yusuke, Nishimasu Hiroshi, Negishi Aina, Paul Sudip Kumar, Takemura Naoki, Satoh Takeshi, Kimura Yasumasa, Kurachi Makoto, Nureki Osamu, Nakai Kenta, Kiyono Hiroshi, Uematsu Satoshi

    International Immunology   30 ( 4 )   141 - 154   2018.04( ISSN:0953-8178

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    Cas9/シングルガイドRNAリボ核蛋白質(RNP)送達を用いた、高結合活性腫瘍抗原特異的細胞傷害性T細胞(CTL)を作製する戦略について検討した。gp100黒色腫関連腫瘍抗原で免疫したマウスから、gp100特異的高結合活性T細胞受容体(TCR)を複製した。また腫瘍抗原特異的TCR/抗原-主要組織適合遺伝子複合体(pMHC)相互作用に対する3D蛋白質構造モデリングシステムを開発し、TCRの迅速な構造詳細分析を可能とした。これら手法の組み合わせで、Cas9RNP送達を用いてgp100特異的PD-1ノックアウトCD8陽性T細胞を効率的に作製可能であった。当該CD8陽性T細胞は、in vitroおよびin vivoで黒色腫細胞に対する高い結合活性を有し、抗腫瘍有効性の増強を示した。ゲノム編集と計算モデリングツールを組み合わせることで、高い特異性を有し安全かつ広範に適用可能な抗癌治療法を開発できることが示された。

  • Eosinophil depletion suppresses radiation-induced small intestinal fibrosis. Reviewed

    Takemura N, Kurashima Y, Mori Y, Okada K, Ogino T, Osawa H, Matsuno H, Aayam L, Kaneto S, Park EJ, Sato S, Matsunaga K, Tamura Y, Ouchi Y, Kumagai Y, Kobayashi D, Suzuki Y, Yoshioka Y, Nishimura J, Mori M, Ishii KJ, Rothenberg ME, Kiyono H, Akira S, Uematsu S

    Science translational medicine   10 ( 429 )   2018.02( ISSN:1946-6234

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    DOI: 10.1126/scitranslmed.aan0333

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  • A Refined Culture System for Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids. Reviewed

    Takahashi Y, Sato S, Kurashima Y, Yamamoto T, Kurokawa S, Yuki Y, Takemura N, Uematsu S, Lai CY, Otsu M, Matsuno H, Osawa H, Mizushima T, Nishimura J, Hayashi M, Yamaguchi T, Kiyono H

    Stem cell reports   10 ( 1 )   314 - 328   2018.01

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    DOI: 10.1016/j.stemcr.2017.11.004

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  • Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis. Reviewed

    Koyanagi N, Imai T, Shindo K, Sato A, Fujii W, Ichinohe T, Takemura N, Kakuta S, Uematsu S, Kiyono H, Maruzuru Y, Arii J, Kato A, Kawaguchi Y

    The Journal of clinical investigation   127 ( 10 )   3784 - 3795   2017.10( ISSN:0021-9738

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    DOI: 10.1172/JCI92931

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  • Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1<sup>+</sup>CXCR5<sup>-/dim</sup> B-helper T cell induction. Reviewed

    Eri T, Kawahata K, Kanzaki T, Imamura M, Michishita K, Akahira L, Bannai E, Yoshikawa N, Kimura Y, Satoh T, Uematsu S, Tanaka H, Yamamoto K

    Scientific reports   7   46037   2017.04

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    DOI: 10.1038/srep46037

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  • G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE2. Reviewed

    Kawano Y, Fukui C, Shinohara M, Wakahashi K, Ishii S, Suzuki T, Sato M, Asada N, Kawano H, Minagawa K, Sada A, Furuyashiki T, Uematsu S, Akira S, Uede T, Narumiya S, Matsui T, Katayama Y

    Blood   129 ( 5 )   587 - 597   2017.02( ISSN:0006-4971

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    DOI: 10.1182/blood-2016-07-725754

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  • Mucosal Mesenchymal Cells: Secondary Barrier and Peripheral Educator for the Gut Immune System. Reviewed

    Kurashima Y, Yamamoto D, Nelson S, Uematsu S, Ernst PB, Nakayama T, Kiyono H

    Frontiers in immunology   8   1787   2017

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    DOI: 10.3389/fimmu.2017.01787

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  • Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation. Reviewed

    Kuroda E, Ozasa K, Temizoz B, Ohata K, Koo CX, Kanuma T, Kusakabe T, Kobari S, Horie M, Morimoto Y, Nakajima S, Kabashima K, Ziegler SF, Iwakura Y, Ise W, Kurosaki T, Nagatake T, Kunisawa J, Takemura N, Uematsu S, Hayashi M, Aoshi T, Kobiyama K, Coban C, Ishii KJ

    Immunity   45 ( 6 )   1299 - 1310   2016.12( ISSN:1074-7613

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    DOI: 10.1016/j.immuni.2016.11.010

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  • Epithelial glycosylation in gut homeostasis and inflammation. Reviewed

    Goto Y, Uematsu S, Kiyono H

    Nature immunology   17 ( 11 )   1244 - 1251   2016.10( ISSN:1529-2908

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    DOI: 10.1038/ni.3587

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  • p53 Is a Host Cell Regulator during Herpes Simplex Encephalitis. Reviewed

    Maruzuru Y, Koyanagi N, Takemura N, Uematsu S, Matsubara D, Suzuki Y, Arii J, Kato A, Kawaguchi Y

    Journal of virology   90 ( 15 )   6738 - 6745   2016.08( ISSN:0022-538X

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    DOI: 10.1128/JVI.00846-16

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  • Isolation and Functional Analysis of Lamina Propria Dendritic Cells from the Mouse Small Intestine. Reviewed

    Takemura N, Uematsu S

    Methods in molecular biology (Clifton, N.J.)   1422   181 - 8   2016( ISSN:1064-3745

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    DOI: 10.1007/978-1-4939-3603-8_17

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  • Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis. Reviewed

    Inada M, Takita M, Yokoyama S, Watanabe K, Tominari T, Matsumoto C, Hirata M, Maru Y, Maruyama T, Sugimoto Y, Narumiya S, Uematsu S, Akira S, Murphy G, Nagase H, Miyaura C

    The Journal of biological chemistry   290 ( 50 )   29781 - 93   2015.12( ISSN:0021-9258

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    DOI: 10.1074/jbc.M115.669481

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  • Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model. Reviewed

    Matsuda H, Hosono K, Tsuru S, Kurashige C, Sekiguchi K, Akira S, Uematsu S, Okamoto H, Majima M

    Life sciences   142   1 - 7   2015.12( ISSN:0024-3205

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    DOI: 10.1016/j.lfs.2015.10.008

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  • Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production. Reviewed

    Flores-Langarica A, Bobat S, Marshall JL, Yam-Puc JC, Cook CN, Serre K, Kingsley RA, Flores-Romo L, Uematsu S, Akira S, Henderson IR, Toellner KM, Cunningham AF

    European journal of immunology   45 ( 8 )   2299 - 311   2015.08( ISSN:0014-2980

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    DOI: 10.1002/eji.201545564

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  • 5-Azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival. Reviewed

    Maruyama K, Fukasaka M, Uematsu S, Takeuchi O, Kondo T, Saitoh T, Martino MM, Akira S

    The Journal of biological chemistry   290 ( 15 )   9377 - 86   2015.04( ISSN:0021-9258

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    DOI: 10.1074/jbc.M114.631374

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  • Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9. Reviewed

    Atif SM, Lee SJ, Li LX, Uematsu S, Akira S, Gorjestani S, Lin X, Schweighoffer E, Tybulewicz VL, McSorley SJ

    European journal of immunology   45 ( 2 )   513 - 24   2015.02( ISSN:0014-2980

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    DOI: 10.1002/eji.201444744

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  • MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus. Reviewed

    Reynolds LA, Harcus Y, Smith KA, Webb LM, Hewitson JP, Ross EA, Brown S, Uematsu S, Akira S, Gray D, Gray M, MacDonald AS, Cunningham AF, Maizels RM

    Journal of immunology (Baltimore, Md. : 1950)   193 ( 6 )   2984 - 93   2014.09( ISSN:0022-1767

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    DOI: 10.4049/jimmunol.1401056

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  • Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Reviewed

    Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Setoyama H, Imaoka A, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H

    Science (New York, N.Y.)   345 ( 6202 )   1254009   2014.09( ISSN:0036-8075

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    DOI: 10.1126/science.1254009

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  • Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Reviewed

    Takemura N, Kawasaki T, Kunisawa J, Sato S, Lamichhane A, Kobiyama K, Aoshi T, Ito J, Mizuguchi K, Karuppuchamy T, Matsunaga K, Miyatake S, Mori N, Tsujimura T, Satoh T, Kumagai Y, Kawai T, Standley DM, Ishii KJ, Kiyono H, Akira S, Uematsu S

    Nature communications   5   3492   2014.03

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    DOI: 10.1038/ncomms4492

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  • Prevention of intestinal allergy in mice by rflaA:Ova is associated with enforced antigen processing and TLR5-dependent IL-10 secretion by mDC. Reviewed

    Schülke S, Wolfheimer S, Gadermaier G, Wangorsch A, Siebeneicher S, Briza P, Spreitzer I, Schiller D, Loeschner B, Uematsu S, Ryffel B, Akira S, Waibler Z, Vieths S, Toda M, Scheurer S

    PloS one   9 ( 2 )   e87822   2014

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    DOI: 10.1371/journal.pone.0087822

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  • Increased Th17-inducing activity of CD14+ CD163 low myeloid cells in intestinal lamina propria of patients with Crohn's disease. Reviewed

    Ogino T, Nishimura J, Barman S, Kayama H, Uematsu S, Okuzaki D, Osawa H, Haraguchi N, Uemura M, Hata T, Takemasa I, Mizushima T, Yamamoto H, Takeda K, Doki Y, Mori M

    Gastroenterology   145 ( 6 )   1380 - 91.e1   2013.12( ISSN:0016-5085

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    DOI: 10.1053/j.gastro.2013.08.049

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  • Prostaglandin E₂ is critical for the development of niacin-deficiency-induced photosensitivity via ROS production. Reviewed

    Sugita K, Ikenouchi-Sugita A, Nakayama Y, Yoshioka H, Nomura T, Sakabe J, Nakahigashi K, Kuroda E, Uematsu S, Nakamura J, Akira S, Nakamura M, Narumiya S, Miyachi Y, Tokura Y, Kabashima K

    Scientific reports   3   2973   2013.10

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    DOI: 10.1038/srep02973

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  • DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant. Reviewed

    Nyström S, Bråve A, Falkeborn T, Devito C, Rissiek B, Johansson DX, Schröder U, Uematsu S, Akira S, Hinkula J, Applequist SE

    Vaccines   1 ( 4 )   415 - 43   2013.09

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    DOI: 10.3390/vaccines1040415

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  • Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP. Reviewed

    Maruyama K, Uematsu S, Kondo T, Takeuchi O, Martino MM, Kawasaki T, Akira S

    The Journal of experimental medicine   210 ( 10 )   1947 - 60   2013.09( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20130512

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  • Flagellin enhances tumor-specific CD8⁺ T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model. Reviewed

    Nguyen CT, Hong SH, Sin JI, Vu HV, Jeong K, Cho KO, Uematsu S, Akira S, Lee SE, Rhee JH

    Vaccine   31 ( 37 )   3879 - 87   2013.08( ISSN:0264-410X

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    DOI: 10.1016/j.vaccine.2013.06.054

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  • Microsomal prostaglandin E synthase-1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease-like pathology in a mouse model. Reviewed

    Akitake Y, Nakatani Y, Kamei D, Hosokawa M, Akatsu H, Uematsu S, Akira S, Kudo I, Hara S, Takahashi M

    Journal of neuroscience research   91 ( 7 )   909 - 19   2013.07( ISSN:0360-4012

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/jnr.23217

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  • Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-β. Reviewed

    Kawashima T, Kosaka A, Yan H, Guo Z, Uchiyama R, Fukui R, Kaneko D, Kumagai Y, You DJ, Carreras J, Uematsu S, Jang MH, Takeuchi O, Kaisho T, Akira S, Miyake K, Tsutsui H, Saito T, Nishimura I, Tsuji NM

    Immunity   38 ( 6 )   1187 - 97   2013.06( ISSN:1074-7613

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    DOI: 10.1016/j.immuni.2013.02.024

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  • Critical role of AZI2 in GM-CSF-induced dendritic cell differentiation. Reviewed

    Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O

    Journal of immunology (Baltimore, Md. : 1950)   190 ( 11 )   5702 - 11   2013.06( ISSN:0022-1767

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    DOI: 10.4049/jimmunol.1203155

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  • Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance Reviewed

    Fujiwara Nagatoshi, Porcelli Steven A., Naka Takashi, Yano Ikuya, Maeda Shinji, Kuwata Hirotaka, Akira Shizuo, Uematsu Satoshi, Takii Takemasa, Ogura Hisashi, Kobayashi Kazuo

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS   1831 ( 6 )   1177 - 1184   2013.06( ISSN:1388-1981

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    DOI: 10.1016/j.bbalip.2013.03.008

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  • Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice. Reviewed

    Kaiko GE, Loh Z, Spann K, Lynch JP, Lalwani A, Zheng Z, Davidson S, Uematsu S, Akira S, Hayball J, Diener KR, Baines KJ, Simpson JL, Foster PS, Phipps S

    The Journal of allergy and clinical immunology   131 ( 5 )   1331 - 9.e10   2013.05( ISSN:0091-6749

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    DOI: 10.1016/j.jaci.2013.02.041

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  • Commensal microbiota drive proliferation of conventional and Foxp3(+) regulatory CD4(+) T cells in mesenteric lymph nodes and Peyer's patches. Reviewed

    Cording S, Fleissner D, Heimesaat MM, Bereswill S, Loddenkemper C, Uematsu S, Akira S, Hamann A, Huehn J

    European journal of microbiology & immunology   3 ( 1 )   1 - 10   2013.03( ISSN:2062-509X

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    DOI: 10.1556/EuJMI.3.2013.1.1

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  • Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis. Reviewed

    Takeuchi C, Matsumoto Y, Kohyama K, Uematsu S, Akira S, Yamagata K, Takemiya T

    Neurochemistry international   62 ( 3 )   271 - 80   2013.02( ISSN:0197-0186

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    DOI: 10.1016/j.neuint.2012.12.007

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  • Systemic flagellin immunization stimulates mucosal CD103+ dendritic cells and drives Foxp3+ regulatory T cell and IgA responses in the mesenteric lymph node. Reviewed

    Flores-Langarica A, Marshall JL, Hitchcock J, Cook C, Jobanputra J, Bobat S, Ross EA, Coughlan RE, Henderson IR, Uematsu S, Akira S, Cunningham AF

    Journal of immunology (Baltimore, Md. : 1950)   189 ( 12 )   5745 - 54   2012.12( ISSN:0022-1767

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    DOI: 10.4049/jimmunol.1202283

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  • PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. Reviewed

    Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K

    International immunology   24 ( 10 )   613 - 23   2012.10( ISSN:0953-8178

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    DOI: 10.1093/intimm/dxs068

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  • 好中球、古典的単球、樹状細胞における細胞表面でのTLR5のPRAT4A依存的発現(PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells) Reviewed

    Shibata Takuma, Takemura Naoki, Motoi Yuji, Goto Yoshiyuki, Karuppuchamy Thangaraj, Izawa Kumi, Li Xiaobing, Akashi-Takamura Sachiko, Tanimura Natsuko, Kunisawa Jun, Kiyono Hiroshi, Akira Shizuo, Kitamura Toshio, Kitaura Jiro, Uematsu Satoshi, Miyake Kensuke

    Oxford University Press International Immunology   24 ( 10 )   613 - 623   2012.10( ISSN:0953-8178

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    抗Toll様受容体(TLR)5モノクローナル抗体を作成し、様々な免疫細胞におけるTLR5細胞表面発現を検討し、TLR5細胞表面発現と応答におけるTLR4A結合蛋白質(PRAT4A)の関与を明らかにした。BALB/cマウスと野生型C57BL/6マウスを用いて、抗マウスTLR5モノクローナル抗体を作成した。マクロファージ細胞株J774は、細胞表面で内因性TLR5を発現し、フラジェリンに反応してIL-6とG-CSFを産生した。TLR5細胞表面発現とフラジェリン誘導反応は、TLR特異的シャペロンPRAT4Aをサイレンシングすることにより完全に消失したことから、TLR5は別のPRAT4Aクライアントであることが示された。in vivo免疫細胞において、細胞表面TLR5は主に骨髄、循環血、脾臓、炎症病変における好中球とCD11bhiLy6Chi古典的単球上で認められた。Ly6Chi古典的単球は、フラジェリンに反応してサイトカインを産生したが、好中球は産生しなかった。脾臓CD8-CD4+樹状細胞とCD11chiCD11bhi固有層樹状細胞も細胞表面でTLR5を発現した。

  • 好中球、古典的単球、樹状細胞における細胞表面でのTLR5のPRAT4A依存的発現(PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells) Reviewed

    Shibata Takuma, Takemura Naoki, Motoi Yuji, Goto Yoshiyuki, Karuppuchamy Thangaraj, Izawa Kumi, Li Xiaobing, Akashi-Takamura Sachiko, Tanimura Natsuko, Kunisawa Jun, Kiyono Hiroshi, Akira Shizuo, Kitamura Toshio, Kitaura Jiro, Uematsu Satoshi, Miyake Kensuke

    International Immunology   24 ( 10 )   613 - 623   2012.10( ISSN:0953-8178

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    抗Toll様受容体(TLR)5モノクローナル抗体を作成し、様々な免疫細胞におけるTLR5細胞表面発現を検討し、TLR5細胞表面発現と応答におけるTLR4A結合蛋白質(PRAT4A)の関与を明らかにした。BALB/cマウスと野生型C57BL/6マウスを用いて、抗マウスTLR5モノクローナル抗体を作成した。マクロファージ細胞株J774は、細胞表面で内因性TLR5を発現し、フラジェリンに反応してIL-6とG-CSFを産生した。TLR5細胞表面発現とフラジェリン誘導反応は、TLR特異的シャペロンPRAT4Aをサイレンシングすることにより完全に消失したことから、TLR5は別のPRAT4Aクライアントであることが示された。in vivo免疫細胞において、細胞表面TLR5は主に骨髄、循環血、脾臓、炎症病変における好中球とCD11bhiLy6Chi古典的単球上で認められた。Ly6Chi古典的単球は、フラジェリンに反応してサイトカインを産生したが、好中球は産生しなかった。脾臓CD8-CD4+樹状細胞とCD11chiCD11bhi固有層樹状細胞も細胞表面でTLR5を発現した。

  • Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31-35. Reviewed

    Kuroki Y, Sasaki Y, Kamei D, Akitake Y, Takahashi M, Uematsu S, Akira S, Nakatani Y, Kudo I, Hara S

    Biochemical and biophysical research communications   424 ( 3 )   409 - 13   2012.08( ISSN:0006-291X

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    DOI: 10.1016/j.bbrc.2012.06.121

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  • Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in the retina and retinal-pigmented epithelium. Reviewed

    Chucair-Elliott AJ, Elliott MH, Wang J, Moiseyev GP, Ma JX, Politi LE, Rotstein NP, Akira S, Uematsu S, Ash JD

    The Journal of biological chemistry   287 ( 29 )   24092 - 102   2012.07( ISSN:0021-9258

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    DOI: 10.1074/jbc.M112.378240

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  • Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice. Reviewed

    Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C

    Toxicological sciences : an official journal of the Society of Toxicology   127 ( 2 )   547 - 54   2012.06( ISSN:1096-6080

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    DOI: 10.1093/toxsci/kfs115

    PubMed

  • Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity. Reviewed

    Kreutz M, Giquel B, Hu Q, Abuknesha R, Uematsu S, Akira S, Nestle FO, Diebold SS

    PloS one   7 ( 7 )   e40208   2012

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    DOI: 10.1371/journal.pone.0040208

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  • The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A. Reviewed

    Moreira AP, Cavassani KA, Ismailoglu UB, Hullinger R, Dunleavy MP, Knight DA, Kunkel SL, Uematsu S, Akira S, Hogaboam CM

    The Journal of clinical investigation   121 ( 11 )   4420 - 32   2011.11( ISSN:0021-9738

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1172/JCI44999

    PubMed

  • A new subset of CD103+CD8alpha+ dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity. Reviewed

    Fujimoto K, Karuppuchamy T, Takemura N, Shimohigoshi M, Machida T, Haseda Y, Aoshi T, Ishii KJ, Akira S, Uematsu S

    Journal of immunology (Baltimore, Md. : 1950)   186 ( 11 )   6287 - 95   2011.06( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.1004036

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  • Plasmacytoid dendritic cells promote host defense against acute pneumovirus infection via the TLR7-MyD88-dependent signaling pathway. Reviewed

    Davidson S, Kaiko G, Loh Z, Lalwani A, Zhang V, Spann K, Foo SY, Hansbro N, Uematsu S, Akira S, Matthaei KI, Rosenberg HF, Foster PS, Phipps S

    Journal of immunology (Baltimore, Md. : 1950)   186 ( 10 )   5938 - 48   2011.05( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.1002635

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  • TLR5-deficient mice lack basal inflammatory and metabolic defects but exhibit impaired CD4 T cell responses to a flagellated pathogen. Reviewed

    Letran SE, Lee SJ, Atif SM, Flores-Langarica A, Uematsu S, Akira S, Cunningham AF, McSorley SJ

    Journal of immunology (Baltimore, Md. : 1950)   186 ( 9 )   5406 - 12   2011.05( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.1003576

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  • Silica crystals and aluminum salts regulate the production of prostaglandin in macrophages via NALP3 inflammasome-independent mechanisms. Reviewed

    Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S, Aritake K, Urade Y, Morimoto Y

    Immunity   34 ( 4 )   514 - 26   2011.04( ISSN:1074-7613

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.immuni.2011.03.019

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  • Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice. Reviewed

    Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S, DeClerck YA, Okamoto H, Majima M

    Life sciences   88 ( 15-16 )   693 - 700   2011.04( ISSN:0024-3205

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.lfs.2011.02.008

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  • Antigen-specific T-cell responses to a recombinant fowlpox virus are dependent on MyD88 and interleukin-18 and independent of Toll-like receptor 7 (TLR7)- and TLR9-mediated innate immune recognition. Reviewed

    Lousberg EL, Diener KR, Fraser CK, Phipps S, Foster PS, Chen W, Uematsu S, Akira S, Robertson SA, Brown MP, Hayball JD

    Journal of virology   85 ( 7 )   3385 - 96   2011.04( ISSN:0022-538X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/JVI.02000-10

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  • Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Reviewed

    Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S

    Immunity   34 ( 3 )   352 - 63   2011.03( ISSN:1074-7613

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.immuni.2011.03.010

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  • 宿主における誘導型prostaglandin E synthase mPGES-1の腫瘍血管新生促進における役割(Roles of an inducible prostaglandin E synthase, mPGES-1 in host in enhancement of tumor-associated angiogenesis) Reviewed

    Kamata Hiroki, Hosono Kanako, Suzuki Tatsunori, Ogawa Yasufumi, Kubo Hidefumi, Katoh Hiroshi, Ito Yoshiya, Uematsu Satoshi, Akira Shizuo, Watanabe Masahiko, Majima Masataka

    北里医学会 The Kitasato Medical Journal   41 ( 1 )   19 - 30   2011.03( ISSN:1349-8568

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    宿主組織中のmicrosomal prostaglandin(PG) E synthase(mPGES)-1の腫瘍血管新生促進における役割について検討した。野生型マウス(WT、C57BL6マウス)と戻し交配した8週齡のmPGES-1ノックアウト(KO)マウス雄を用いた。ルイス肺がん(LLC)細胞をマウスの背側の皮下組織内に注入した。腫瘍の増殖を経時的に評価した。連続切片をhematoxylin and eosin(H&E)で染色した。微小血管密度(MVD)および微小血管面積(MVA)を血管新生のパラメータとして測定した。高線量照射したWTマウスを2群に分けた。大腿骨、脛骨、骨盤からそれぞれ採取したmPGES-1骨髄(BM)細胞を、放射線照射したWTマウスに尾静脈から注入した。別の群には、WTマウス由来のBM細胞を注入した。血管新生も評価した。mPGES-1 KOマウス(mPGES-1-/-)における増殖および腫瘍血管新生は、WTマウスと比較して、LCC細胞の皮下注入後に抑制された。致死線量の照射後、WTのBM細胞をmPGES-1-/-から単離したBM細胞と置換した。mPGES-1-/-BMキメラマウスにおいて測定したスポンジインプラント内の血管新生レベルは、WTBMキメラマウスと比較して有意に低下していた。組織検査で評価した腫瘍血管新生は、腫瘍間質に限局しており、mPGES-1-/-BMキメラマウスにおいてWT BMキメラマウスよりも有意に抑制されていた。免疫組織化学検査により評価した腫瘍切片から、間質組織中の血管内皮増殖因子(VEGF)がmPGES-1-/-BMキメラマウスにおいて野生型BMキメラマウスよりも顕著に低かったことが示された。宿主のmPGES-1が腫瘍血管新生を促進させることや、mPGES-1を発現するBM細胞の原発腫瘍部位への動員の調節が固形腫瘍の新しい治療法となる可能性を示唆していた。

  • Endothelial microsomal prostaglandin E synthase-1 facilitates neurotoxicity by elevating astrocytic Ca2+ levels. Reviewed

    Takemiya T, Matsumura K, Sugiura H, Yasuda S, Uematsu S, Akira S, Yamagata K

    Neurochemistry international   58 ( 4 )   489 - 96   2011.03( ISSN:0197-0186

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.neuint.2011.01.003

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  • 宿主における誘導型prostaglandin E synthase mPGES-1の腫瘍血管新生促進における役割(Roles of an inducible prostaglandin E synthase, mPGES-1 in host in enhancement of tumor-associated angiogenesis) Reviewed

    Kamata Hiroki, Hosono Kanako, Suzuki Tatsunori, Ogawa Yasufumi, Kubo Hidefumi, Katoh Hiroshi, Ito Yoshiya, Uematsu Satoshi, Akira Shizuo, Watanabe Masahiko, Majima Masataka

    The Kitasato Medical Journal   41 ( 1 )   19 - 30   2011.03( ISSN:1349-8568

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    Publishing type:Research paper (scientific journal)  

    宿主組織中のmicrosomal prostaglandin(PG) E synthase(mPGES)-1の腫瘍血管新生促進における役割について検討した。野生型マウス(WT、C57BL6マウス)と戻し交配した8週齡のmPGES-1ノックアウト(KO)マウス雄を用いた。ルイス肺がん(LLC)細胞をマウスの背側の皮下組織内に注入した。腫瘍の増殖を経時的に評価した。連続切片をhematoxylin and eosin(H&E)で染色した。微小血管密度(MVD)および微小血管面積(MVA)を血管新生のパラメータとして測定した。高線量照射したWTマウスを2群に分けた。大腿骨、脛骨、骨盤からそれぞれ採取したmPGES-1骨髄(BM)細胞を、放射線照射したWTマウスに尾静脈から注入した。別の群には、WTマウス由来のBM細胞を注入した。血管新生も評価した。mPGES-1 KOマウス(mPGES-1-/-)における増殖および腫瘍血管新生は、WTマウスと比較して、LCC細胞の皮下注入後に抑制された。致死線量の照射後、WTのBM細胞をmPGES-1-/-から単離したBM細胞と置換した。mPGES-1-/-BMキメラマウスにおいて測定したスポンジインプラント内の血管新生レベルは、WTBMキメラマウスと比較して有意に低下していた。組織検査で評価した腫瘍血管新生は、腫瘍間質に限局しており、mPGES-1-/-BMキメラマウスにおいてWT BMキメラマウスよりも有意に抑制されていた。免疫組織化学検査により評価した腫瘍切片から、間質組織中の血管内皮増殖因子(VEGF)がmPGES-1-/-BMキメラマウスにおいて野生型BMキメラマウスよりも顕著に低かったことが示された。宿主のmPGES-1が腫瘍血管新生を促進させることや、mPGES-1を発現するBM細胞の原発腫瘍部位への動員の調節が固形腫瘍の新しい治療法となる可能性を示唆していた。

  • The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model. Reviewed

    Numao A, Hosono K, Suzuki T, Hayashi I, Uematsu S, Akira S, Ogino Y, Kawauchi H, Unno N, Majima M

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   65 ( 1 )   77 - 84   2011.02( ISSN:0753-3322

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.biopha.2010.12.008

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  • Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. Reviewed

    Seo SU, Kwon HJ, Ko HJ, Byun YH, Seong BL, Uematsu S, Akira S, Kweon MN

    PLoS pathogens   7 ( 2 )   e1001304   2011.02( ISSN:1553-7366

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.ppat.1001304

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  • Airway epithelial indoleamine 2,3-dioxygenase inhibits CD4+ T cells during Aspergillus fumigatus antigen exposure. Reviewed

    Paveglio SA, Allard J, Foster Hodgkins SR, Ather JL, Bevelander M, Campbell JM, Whittaker LeClair LA, McCarthy SM, van der Vliet A, Suratt BT, Boyson JE, Uematsu S, Akira S, Poynter ME

    American journal of respiratory cell and molecular biology   44 ( 1 )   11 - 23   2011.01( ISSN:1044-1549

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1165/rcmb.2009-0167OC

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  • TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Reviewed

    Letran SE, Lee SJ, Atif SM, Uematsu S, Akira S, McSorley SJ

    European journal of immunology   41 ( 1 )   29 - 38   2011.01( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.201040717

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  • Role of adrenomedullin in Lyme disease. Reviewed

    Marre ML, Darcy CT, Yinh J, Akira S, Uematsu S, Steere AC, Hu LT

    Infection and immunity   78 ( 12 )   5307 - 13   2010.12( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.00630-10

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  • Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes. Reviewed

    Abe Y, Kawakami A, Osaka M, Uematsu S, Akira S, Shimokado K, Sacks FM, Yoshida M

    Arteriosclerosis, thrombosis, and vascular biology   30 ( 11 )   2242 - 8   2010.11( ISSN:1079-5642

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1161/ATVBAHA.110.210427

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  • The innate immune system in the intestine. Reviewed

    Uematsu S, Fujimoto K

    Microbiology and immunology   54 ( 11 )   645 - 57   2010.11( ISSN:0385-5600

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1348-0421.2010.00267.x

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  • Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers. Reviewed

    Ae T, Ohno T, Hattori Y, Suzuki T, Hosono K, Minamino T, Sato T, Uematsu S, Akira S, Koizumi W, Majima M

    American journal of physiology. Gastrointestinal and liver physiology   299 ( 5 )   G1139 - 46   2010.11( ISSN:0193-1857

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1152/ajpgi.00013.2010

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  • Pathways regulating cytosolic phospholipase A2 activation and eicosanoid production in macrophages by Candida albicans. Reviewed

    Suram S, Gangelhoff TA, Taylor PR, Rosas M, Brown GD, Bonventre JV, Akira S, Uematsu S, Williams DL, Murphy RC, Leslie CC

    The Journal of biological chemistry   285 ( 40 )   30676 - 85   2010.10( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M110.143800

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  • mPGES-1-expressing bone marrow-derived cells enhance tumor growth and angiogenesis in mice. Reviewed

    Kamata H, Hosono K, Suzuki T, Ogawa Y, Kubo H, Katoh H, Ito Y, Uematsu S, Akira S, Watanabe M, Majima M

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   64 ( 6 )   409 - 16   2010.07( ISSN:0753-3322

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.biopha.2010.01.017

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  • Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice. Reviewed

    Santiago-Raber ML, Dunand-Sauthier I, Wu T, Li QZ, Uematsu S, Akira S, Reith W, Mohan C, Kotzin BL, Izui S

    Journal of autoimmunity   34 ( 4 )   339 - 48   2010.06( ISSN:0896-8411

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jaut.2009.11.001

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  • Toll-like receptor 7 (TLR7) modulates anti-nucleosomal autoantibody isotype and renal complement deposition in mice exposed to syngeneic late apoptotic cells. Reviewed

    Pan ZJ, Maier S, Schwarz K, Azbill J, Akira S, Uematsu S, Farris AD

    Annals of the rheumatic diseases   69 ( 6 )   1195 - 9   2010.06( ISSN:0003-4967

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    DOI: 10.1136/ard.2009.108282

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  • Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide-binding oligomerization domain-mediated NF-kappa B signaling. Reviewed

    Toma C, Higa N, Koizumi Y, Nakasone N, Ogura Y, McCoy AJ, Franchi L, Uematsu S, Sagara J, Taniguchi S, Tsutsui H, Akira S, Tschopp J, Núñez G, Suzuki T

    Journal of immunology (Baltimore, Md. : 1950)   184 ( 9 )   5287 - 97   2010.05( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0903536

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  • Toll-like receptor 6 drives interleukin-17A expression during experimental hypersensitivity pneumonitis. Reviewed

    Fong DJ, Hogaboam CM, Matsuno Y, Akira S, Uematsu S, Joshi AD

    Immunology   130 ( 1 )   125 - 36   2010.05( ISSN:0019-2805

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2567.2009.03219.x

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  • Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists. Reviewed

    Rajagopal D, Paturel C, Morel Y, Uematsu S, Akira S, Diebold SS

    Blood   115 ( 10 )   1949 - 57   2010.03( ISSN:0006-4971

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-08-238543

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  • TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas MyD88 is required to clear infection. Reviewed

    Burns E, Eliyahu T, Uematsu S, Akira S, Nussbaum G

    Journal of immunology (Baltimore, Md. : 1950)   184 ( 3 )   1455 - 62   2010.02( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0900378

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  • Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate. Reviewed

    Takemiya T, Matsumura K, Sugiura H, Maehara M, Yasuda S, Uematsu S, Akira S, Yamagata K

    Journal of neuroscience research   88 ( 2 )   381 - 90   2010.02( ISSN:0360-4012

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/jnr.22195

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  • Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation. Reviewed

    Lundequist A, Nallamshetty SN, Xing W, Feng C, Laidlaw TM, Uematsu S, Akira S, Boyce JA

    Journal of immunology (Baltimore, Md. : 1950)   184 ( 1 )   433 - 41   2010.01( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0902835

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  • Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis. Reviewed

    Kamei D, Murakami M, Sasaki Y, Nakatani Y, Majima M, Ishikawa Y, Ishii T, Uematsu S, Akira S, Hara S, Kudo I

    The Biochemical journal   425 ( 2 )   361 - 71   2009.12( ISSN:0264-6021

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1042/BJ20090045

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  • Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis. Reviewed

    Kihara Y, Matsushita T, Kita Y, Uematsu S, Akira S, Kira J, Ishii S, Shimizu T

    Proceedings of the National Academy of Sciences of the United States of America   106 ( 51 )   21807 - 12   2009.12( ISSN:0027-8424

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.0906891106

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  • Baculovirus induces type I interferon production through toll-like receptor-dependent and -independent pathways in a cell-type-specific manner. Reviewed

    Abe T, Kaname Y, Wen X, Tani H, Moriishi K, Uematsu S, Takeuchi O, Ishii KJ, Kawai T, Akira S, Matsuura Y

    Journal of virology   83 ( 15 )   7629 - 40   2009.08( ISSN:0022-538X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/JVI.00679-09

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  • Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K. Reviewed

    Shin OS, Miller LS, Modlin RL, Akira S, Uematsu S, Hu LT

    Journal of immunology (Baltimore, Md. : 1950)   183 ( 1 )   491 - 8   2009.07( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0900724

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  • PolyI:C-induced reduction in uptake of soluble antigen is independent of dendritic cell activation. Reviewed

    Tirapu I, Giquel B, Alexopoulou L, Uematsu S, Flavell R, Akira S, Diebold SS

    International immunology   21 ( 7 )   871 - 9   2009.07( ISSN:0953-8178

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxp053

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  • NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection. Reviewed

    Kayama H, Koga R, Atarashi K, Okuyama M, Kimura T, Mak TW, Uematsu S, Akira S, Takayanagi H, Honda K, Yamamoto M, Takeda K

    PLoS pathogens   5 ( 7 )   e1000514   2009.07( ISSN:1553-7366

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.ppat.1000514

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  • Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin. Reviewed

    Bates JT, Uematsu S, Akira S, Mizel SB

    Journal of immunology (Baltimore, Md. : 1950)   182 ( 12 )   7539 - 47   2009.06( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0804225

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  • [TLR5+ DC-mediated immune response to bacterial infection in the intestine]. Reviewed

    Uematsu S

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   54 ( 8 Suppl )   1020 - 6   2009.06( ISSN:0039-9450

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    Publishing type:Research paper (scientific journal)   Kind of work:Single Work  

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  • Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin. Reviewed

    Janot L, Sirard JC, Secher T, Noulin N, Fick L, Akira S, Uematsu S, Didierlaurent A, Hussell T, Ryffel B, Erard F

    European journal of immunology   39 ( 6 )   1587 - 96   2009.06( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200838907

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  • Toll-like receptor 3 enhances late-phase reaction of experimental allergic conjunctivitis. Reviewed

    Ueta M, Uematsu S, Akira S, Kinoshita S

    The Journal of allergy and clinical immunology   123 ( 5 )   1187 - 9   2009.05( ISSN:0091-6749

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jaci.2009.03.008

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  • Pivotal Advance: Toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis. Reviewed

    Amiel E, Alonso A, Uematsu S, Akira S, Poynter ME, Berwin B

    Journal of leukocyte biology   85 ( 4 )   595 - 605   2009.04( ISSN:0741-5400

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1189/jlb.1008631

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  • Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease. Reviewed

    Puliti M, Uematsu S, Akira S, Bistoni F, Tissi L

    Infection and immunity   77 ( 4 )   1524 - 31   2009.04( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.00965-08

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  • Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products. Reviewed

    Allard JB, Rinaldi L, Wargo MJ, Allen G, Akira S, Uematsu S, Poynter ME, Hogan DA, Rincon M, Whittaker LA

    European journal of immunology   39 ( 3 )   776 - 88   2009.03( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200838932

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  • Bacterial endotoxin induces the release of high mobility group box 1 via the IFN-beta signaling pathway. Reviewed

    Kim JH, Kim SJ, Lee IS, Lee MS, Uematsu S, Akira S, Oh KI

    Journal of immunology (Baltimore, Md. : 1950)   182 ( 4 )   2458 - 66   2009.02( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.0801364

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  • Induction of adaptive immunity by flagellin does not require robust activation of innate immunity. Reviewed

    Sanders CJ, Franchi L, Yarovinsky F, Uematsu S, Akira S, Núñez G, Gewirtz AT

    European journal of immunology   39 ( 2 )   359 - 71   2009.02( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200838804

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  • Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection. Reviewed

    Uematsu S, Akira S

    Journal of gastroenterology   44 ( 8 )   803 - 11   2009( ISSN:0944-1174

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00535-009-0094-y

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  • Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Reviewed

    Kawakami A, Osaka M, Aikawa M, Uematsu S, Akira S, Libby P, Shimokado K, Sacks FM, Yoshida M

    Circulation research   103 ( 12 )   1402 - 9   2008.12( ISSN:0009-7330

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1161/CIRCRESAHA.108.178426

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  • MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. Reviewed

    Sheahan T, Morrison TE, Funkhouser W, Uematsu S, Akira S, Baric RS, Heise MT

    PLoS pathogens   4 ( 12 )   e1000240   2008.12( ISSN:1553-7366

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.ppat.1000240

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  • Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Reviewed

    Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S

    Nature   456 ( 7219 )   264 - 8   2008.11( ISSN:0028-0836

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature07383

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  • Role of microsomal prostaglandin E synthase-1 (mPGES1)-derived PGE2 in patency of the ductus arteriosus in the mouse. Reviewed

    Baragatti B, Sodini D, Uematsu S, Coceani F

    Pediatric research   64 ( 5 )   523 - 7   2008.11( ISSN:0031-3998

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1203/PDR.0b013e318184d29c

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  • Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines. Reviewed

    Zhu Q, Egelston C, Vivekanandhan A, Uematsu S, Akira S, Klinman DM, Belyakov IM, Berzofsky JA

    Proceedings of the National Academy of Sciences of the United States of America   105 ( 42 )   16260 - 5   2008.10( ISSN:0027-8424

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.0805325105

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  • Evidence for genes in addition to Tlr7 in the Yaa translocation linked with acceleration of systemic lupus erythematosus. Reviewed

    Santiago-Raber ML, Kikuchi S, Borel P, Uematsu S, Akira S, Kotzin BL, Izui S

    Journal of immunology (Baltimore, Md. : 1950)   181 ( 2 )   1556 - 62   2008.07( ISSN:0022-1767

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  • Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Reviewed

    Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S

    Nature immunology   9 ( 7 )   769 - 76   2008.07( ISSN:1529-2908

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ni.1622

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  • Distinct roles for MyD88 and Toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction. Reviewed

    Shin OS, Isberg RR, Akira S, Uematsu S, Behera AK, Hu LT

    Infection and immunity   76 ( 6 )   2341 - 51   2008.06( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.01600-07

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  • Cutting edge: Overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. Reviewed

    Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, Akira S, Alexopoulou L, Dalod M

    Journal of immunology (Baltimore, Md. : 1950)   180 ( 9 )   5799 - 803   2008.05( ISSN:0022-1767

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  • Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells. Reviewed

    Hirata N, Yanagawa Y, Ebihara T, Seya T, Uematsu S, Akira S, Hayashi F, Iwabuchi K, Onoé K

    Molecular immunology   45 ( 10 )   2734 - 42   2008.05( ISSN:0161-5890

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.molimm.2008.02.010

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  • TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. Reviewed

    Zhang B, Ramesh G, Uematsu S, Akira S, Reeves WB

    Journal of the American Society of Nephrology : JASN   19 ( 5 )   923 - 32   2008.05( ISSN:1046-6673

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1681/ASN.2007090982

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  • Toll-like receptor 5-deficient mice have dysregulated intestinal gene expression and nonspecific resistance to Salmonella-induced typhoid-like disease. Reviewed

    Vijay-Kumar M, Aitken JD, Kumar A, Neish AS, Uematsu S, Akira S, Gewirtz AT

    Infection and immunity   76 ( 3 )   1276 - 81   2008.03( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.01491-07

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  • Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2. Reviewed

    Noor S, Goldfine H, Tucker DE, Suram S, Lenz LL, Akira S, Uematsu S, Girotti M, Bonventre JV, Breuel K, Williams DL, Leslie CC

    The Journal of biological chemistry   283 ( 8 )   4744 - 55   2008.02( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M709956200

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  • TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Reviewed

    Ishii KJ, Kawagoe T, Koyama S, Matsui K, Kumar H, Kawai T, Uematsu S, Takeuchi O, Takeshita F, Coban C, Akira S

    Nature   451 ( 7179 )   725 - 9   2008.02( ISSN:0028-0836

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature06537

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  • Colonic patches direct the cross-talk between systemic compartments and large intestine independently of innate immunity. Reviewed

    Chang SY, Cha HR, Uematsu S, Akira S, Igarashi O, Kiyono H, Kweon MN

    Journal of immunology (Baltimore, Md. : 1950)   180 ( 3 )   1609 - 18   2008.02( ISSN:0022-1767

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  • [Innate immunity and tuberculosis]. Reviewed

    Uematsu S, Akira S

    Kekkaku : [Tuberculosis]   83 ( 2 )   101 - 9   2008.02( ISSN:0022-9776

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  • Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase-1 expression in murine microglia by glioma-derived soluble factors. Laboratory investigation. Reviewed

    Nakano Y, Kuroda E, Kito T, Uematsu S, Akira S, Yokota A, Nishizawa S, Yamashita U

    Journal of neurosurgery   108 ( 2 )   311 - 9   2008.02( ISSN:0022-3085

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3171/JNS/2008/108/2/0311

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  • Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders. Reviewed

    Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H

    Arthritis and rheumatism   58 ( 1 )   172 - 83   2008.01( ISSN:0004-3591

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/art.23158

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  • Toll-Like receptors (TLRs) and their ligands. Reviewed

    Uematsu S, Akira S

    Handbook of experimental pharmacology   ( 183 )   1 - 20   2008( ISSN:0171-2004

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/978-3-540-72167-3_1

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  • Deletion of TLR5 results in spontaneous colitis in mice. Reviewed

    Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S, Akira S, Williams IR, Gewirtz AT

    The Journal of clinical investigation   117 ( 12 )   3909 - 21   2007.12( ISSN:0021-9738

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1172/JCI33084

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  • Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila. Reviewed

    Hawn TR, Berrington WR, Smith IA, Uematsu S, Akira S, Aderem A, Smith KD, Skerrett SJ

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 10 )   6981 - 7   2007.11( ISSN:0022-1767

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  • The C/EBP beta isoform 34-kDa LAP is responsible for NF-IL-6-mediated gene induction in activated macrophages, but is not essential for intracellular bacteria killing. Reviewed

    Uematsu S, Kaisho T, Tanaka T, Matsumoto M, Yamakami M, Omori H, Yamamoto M, Yoshimori T, Akira S

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 8 )   5378 - 86   2007.10( ISSN:0022-1767

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  • Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. Reviewed

    Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, Kawai T, Akira S

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 7 )   4711 - 20   2007.10( ISSN:0022-1767

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  • Nitrogen dioxide promotes allergic sensitization to inhaled antigen. Reviewed

    Bevelander M, Mayette J, Whittaker LA, Paveglio SA, Jones CC, Robbins J, Hemenway D, Akira S, Uematsu S, Poynter ME

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 6 )   3680 - 8   2007.09( ISSN:0022-1767

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  • Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency. Reviewed

    Yamamoto M, Uematsu S, Okamoto T, Matsuura Y, Sato S, Kumar H, Satoh T, Saitoh T, Takeda K, Ishii KJ, Takeuchi O, Kawai T, Akira S

    The Journal of experimental medicine   204 ( 9 )   2233 - 9   2007.09( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20070183

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  • Lymphoma immunotherapy with CpG oligodeoxynucleotides requires TLR9 either in the host or in the tumor itself. Reviewed

    Li J, Song W, Czerwinski DK, Varghese B, Uematsu S, Akira S, Krieg AM, Levy R

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 4 )   2493 - 500   2007.08( ISSN:0022-1767

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  • [Toll-like receptor and innate immunity]. Reviewed

    Uematsu S, Akira S

    Seikagaku. The Journal of Japanese Biochemical Society   79 ( 8 )   769 - 76   2007.08( ISSN:0037-1017

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  • IL-3 is an important differentiation factor for the development of prostaglandin E2-producing macrophages between C57BL/6 and BALB/c mice. Reviewed

    Kuroda E, Noguchi J, Doi T, Uematsu S, Akira S, Yamashita U

    European journal of immunology   37 ( 8 )   2185 - 95   2007.08( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200737041

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  • Blocking of the TLR5 activation domain hampers protective potential of flagellin DNA vaccine. Reviewed

    Saha S, Takeshita F, Matsuda T, Jounai N, Kobiyama K, Matsumoto T, Sasaki S, Yoshida A, Xin KQ, Klinman DM, Uematsu S, Ishii KJ, Akira S, Okuda K

    Journal of immunology (Baltimore, Md. : 1950)   179 ( 2 )   1147 - 54   2007.07( ISSN:0022-1767

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  • Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice. Reviewed

    Ramesh G, Zhang B, Uematsu S, Akira S, Reeves WB

    American journal of physiology. Renal physiology   293 ( 1 )   F325 - 32   2007.07( ISSN:1931-857X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1152/ajprenal.00158.2007

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  • Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a. Reviewed

    Shim DH, Chang SY, Park SM, Jang H, Carbis R, Czerkinsky C, Uematsu S, Akira S, Kweon MN

    Vaccine   25 ( 25 )   4828 - 36   2007.06( ISSN:0264-410X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.vaccine.2007.03.050

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  • Toll-like receptors and Type I interferons. Reviewed

    Uematsu S, Akira S

    The Journal of biological chemistry   282 ( 21 )   15319 - 23   2007.05( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.R700009200

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  • Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling. Reviewed

    Kawagoe T, Sato S, Jung A, Yamamoto M, Matsui K, Kato H, Uematsu S, Takeuchi O, Akira S

    The Journal of experimental medicine   204 ( 5 )   1013 - 24   2007.05( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20061523

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  • Deficiencies of myeloid differentiation factor 88, Toll-like receptor 2 (TLR2), or TLR4 produce specific defects in macrophage cytokine secretion induced by Helicobacter pylori. Reviewed

    Obonyo M, Sabet M, Cole SP, Ebmeyer J, Uematsu S, Akira S, Guiney DG

    Infection and immunity   75 ( 5 )   2408 - 14   2007.05( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.01794-06

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  • Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection. Reviewed

    Andersen-Nissen E, Hawn TR, Smith KD, Nachman A, Lampano AE, Uematsu S, Akira S, Aderem A

    Journal of immunology (Baltimore, Md. : 1950)   178 ( 8 )   4717 - 20   2007.04( ISSN:0022-1767

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  • TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses. Reviewed

    Heer AK, Shamshiev A, Donda A, Uematsu S, Akira S, Kopf M, Marsland BJ

    Journal of immunology (Baltimore, Md. : 1950)   178 ( 4 )   2182 - 91   2007.02( ISSN:0022-1767

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  • Pathological role of Toll-like receptor signaling in cerebral malaria. Reviewed

    Coban C, Ishii KJ, Uematsu S, Arisue N, Sato S, Yamamoto M, Kawai T, Takeuchi O, Hisaeda H, Horii T, Akira S

    International immunology   19 ( 1 )   67 - 79   2007.01( ISSN:0953-8178

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxl123

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  • VP1686, a Vibrio type III secretion protein, induces toll-like receptor-independent apoptosis in macrophage through NF-kappaB inhibition. Reviewed

    Bhattacharjee RN, Park KS, Kumagai Y, Okada K, Yamamoto M, Uematsu S, Matsui K, Kumar H, Kawai T, Iida T, Honda T, Takeuchi O, Akira S

    The Journal of biological chemistry   281 ( 48 )   36897 - 904   2006.12( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M605493200

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  • Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling. Reviewed

    Yamamoto M, Sato S, Saitoh T, Sakurai H, Uematsu S, Kawai T, Ishii KJ, Takeuchi O, Akira S

    Journal of immunology (Baltimore, Md. : 1950)   177 ( 11 )   7520 - 4   2006.12( ISSN:0022-1767

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  • Cutting edge: Role of TANK-binding kinase 1 and inducible IkappaB kinase in IFN responses against viruses in innate immune cells. Reviewed

    Matsui K, Kumagai Y, Kato H, Sato S, Kawagoe T, Uematsu S, Takeuchi O, Akira S

    Journal of immunology (Baltimore, Md. : 1950)   177 ( 9 )   5785 - 9   2006.11( ISSN:0022-1767

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  • Intact TRL 9 and type I interferon signaling pathways are required to augment HSV-1 induced corneal CXCL9 and CXCL10. Reviewed

    Wuest T, Austin BA, Uematsu S, Thapa M, Akira S, Carr DJ

    Journal of neuroimmunology   179 ( 1-2 )   46 - 52   2006.10( ISSN:0165-5728

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jneuroim.2006.06.020

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  • Toll-like receptors and innate immunity. Reviewed

    Uematsu S, Akira S

    Journal of molecular medicine (Berlin, Germany)   84 ( 9 )   712 - 25   2006.09( ISSN:0946-2716

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00109-006-0084-y

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  • Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Reviewed

    Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, Saitoh T, Yamamoto N, Sakurai H, Ishii KJ, Yamaoka S, Kawai T, Matsuura Y, Takeuchi O, Akira S

    Nature immunology   7 ( 9 )   962 - 70   2006.09( ISSN:1529-2908

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ni1367

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  • Toxoplasma gondii genotype determines MyD88-dependent signaling in infected macrophages. Reviewed

    Kim L, Butcher BA, Lee CW, Uematsu S, Akira S, Denkers EY

    Journal of immunology (Baltimore, Md. : 1950)   177 ( 4 )   2584 - 91   2006.08( ISSN:0022-1767

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  • Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblast plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation. Reviewed

    Inada M, Matsumoto C, Uematsu S, Akira S, Miyaura C

    Journal of immunology (Baltimore, Md. : 1950)   177 ( 3 )   1879 - 85   2006.08( ISSN:0022-1767

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  • Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury. Reviewed

    Ikeda-Matsuo Y, Ota A, Fukada T, Uematsu S, Akira S, Sasaki Y

    Proceedings of the National Academy of Sciences of the United States of America   103 ( 31 )   11790 - 5   2006.08( ISSN:0027-8424

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.0604400103

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  • CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation. Reviewed

    Shirakawa K, Maeda S, Gotoh T, Hayashi M, Shinomiya K, Ehata S, Nishimura R, Mori M, Onozaki K, Hayashi H, Uematsu S, Akira S, Ogata E, Miyazono K, Imamura T

    Molecular and cellular biology   26 ( 16 )   6105 - 16   2006.08( ISSN:0270-7306

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/MCB.02429-05

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  • Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Reviewed

    Uematsu S, Jang MH, Chevrier N, Guo Z, Kumagai Y, Yamamoto M, Kato H, Sougawa N, Matsui H, Kuwata H, Hemmi H, Coban C, Kawai T, Ishii KJ, Takeuchi O, Miyasaka M, Takeda K, Akira S

    Nature immunology   7 ( 8 )   868 - 74   2006.08( ISSN:1529-2908

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ni1362

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  • Essential role of IPS-1 in innate immune responses against RNA viruses. Reviewed

    Kumar H, Kawai T, Kato H, Sato S, Takahashi K, Coban C, Yamamoto M, Uematsu S, Ishii KJ, Takeuchi O, Akira S

    The Journal of experimental medicine   203 ( 7 )   1795 - 803   2006.07( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20060792

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  • Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin alpha 3 beta 1. Reviewed

    Behera AK, Hildebrand E, Uematsu S, Akira S, Coburn J, Hu LT

    Journal of immunology (Baltimore, Md. : 1950)   177 ( 1 )   657 - 64   2006.07( ISSN:0022-1767

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  • Activation of smooth muscle and myenteric plexus cells of jejunum via Toll-like receptor 4. Reviewed

    Rumio C, Besusso D, Arnaboldi F, Palazzo M, Selleri S, Gariboldi S, Akira S, Uematsu S, Bignami P, Ceriani V, Ménard S, Balsari A

    Journal of cellular physiology   208 ( 1 )   47 - 54   2006.07( ISSN:0021-9541

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/jcp.20632

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  • TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. Reviewed

    Cottalorda A, Verschelde C, Marçais A, Tomkowiak M, Musette P, Uematsu S, Akira S, Marvel J, Bonnefoy-Berard N

    European journal of immunology   36 ( 7 )   1684 - 93   2006.07( ISSN:0014-2980

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200636181

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  • [Innate immunity and toll-like receptor]. Reviewed

    Uematsu S, Akira S

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   95 ( 6 )   1115 - 21   2006.06( ISSN:0021-5384

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  • [Innate immune recognition of viral infection]. Reviewed

    Uematsu S, Akira S

    Uirusu   56 ( 1 )   1 - 8   2006.06( ISSN:0042-6857

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  • Oral and intraperitoneal administration of phosphorothioate oligodeoxynucleotides leads to control of Cryptosporidium parvum infection in neonatal mice. Reviewed

    Barrier M, Lacroix-Lamandé S, Mancassola R, Auray G, Bernardet N, Chaussé AM, Uematsu S, Akira S, Laurent F

    The Journal of infectious diseases   193 ( 10 )   1400 - 7   2006.05( ISSN:0022-1899

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1086/503748

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  • Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Reviewed

    Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S

    Nature   441 ( 7089 )   101 - 5   2006.05( ISSN:0028-0836

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature04734

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  • Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor. Reviewed

    Suram S, Brown GD, Ghosh M, Gordon S, Loper R, Taylor PR, Akira S, Uematsu S, Williams DL, Leslie CC

    The Journal of biological chemistry   281 ( 9 )   5506 - 14   2006.03( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M509824200

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  • The role of Toll-like receptors in immune disorders. Reviewed

    Uematsu S, Akira S

    Expert opinion on biological therapy   6 ( 3 )   203 - 14   2006.03( ISSN:1471-2598

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1517/14712598.6.3.203

    PubMed

  • MyD88 deficiency results in tissue-specific changes in cytokine induction and inflammation in interleukin-18-independent mice infected with Borrelia burgdorferi. Reviewed

    Behera AK, Hildebrand E, Bronson RT, Perides G, Uematsu S, Akira S, Hu LT

    Infection and immunity   74 ( 3 )   1462 - 70   2006.03( ISSN:0019-9567

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.74.3.1462-1470.2006

    PubMed

  • Pathogen recognition and innate immunity. Reviewed

    Akira S, Uematsu S, Takeuchi O

    Cell   124 ( 4 )   783 - 801   2006.02( ISSN:0092-8674

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cell.2006.02.015

    PubMed

  • A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Reviewed

    Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sato S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S

    Nature immunology   7 ( 1 )   40 - 8   2006.01( ISSN:1529-2908

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ni1282

    PubMed

  • 'Toll' gates for future immunotherapy. Reviewed

    Ishii KJ, Uematsu S, Akira S

    Current pharmaceutical design   12 ( 32 )   4135 - 42   2006( ISSN:1381-6128

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    PubMed

  • Escherichia coli verotoxin 1 mediates apoptosis in human HCT116 colon cancer cells by inducing overexpression of the GADD family of genes and S phase arrest. Reviewed

    Bhattacharjee RN, Park KS, Uematsu S, Okada K, Hoshino K, Takeda K, Takeuchi O, Akira S, Iida T, Honda T

    FEBS letters   579 ( 29 )   6604 - 10   2005.12( ISSN:0014-5793

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.febslet.2005.10.053

    PubMed

  • Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. Reviewed

    Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, Chang B, Duramad O, Coffman RL

    The Journal of experimental medicine   202 ( 8 )   1131 - 9   2005.10( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20050914

    PubMed

  • Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum. Reviewed

    Baratin M, Roetynck S, Lépolard C, Falk C, Sawadogo S, Uematsu S, Akira S, Ryffel B, Tiraby JG, Alexopoulou L, Kirschning CJ, Gysin J, Vivier E, Ugolini S

    Proceedings of the National Academy of Sciences of the United States of America   102 ( 41 )   14747 - 52   2005.10( ISSN:0027-8424

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.0507355102

    PubMed

  • Microarray analysis identifies apoptosis regulatory gene expression in HCT116 cells infected with thermostable direct hemolysin-deletion mutant of Vibrio parahaemolyticus. Reviewed

    Bhattacharjee RN, Park KS, Okada K, Kumagai Y, Uematsu S, Takeuchi O, Akira S, Iida T, Honda T

    Biochemical and biophysical research communications   335 ( 2 )   328 - 34   2005.09( ISSN:0006-291X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2005.07.080

    PubMed

  • Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. Reviewed

    Ikeda-Matsuo Y, Ikegaya Y, Matsuki N, Uematsu S, Akira S, Sasaki Y

    Journal of neurochemistry   94 ( 6 )   1546 - 58   2005.09( ISSN:0022-3042

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1471-4159.2005.03302.x

    PubMed

  • Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Reviewed

    de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE

    Nature immunology   6 ( 8 )   844 - 51   2005.08( ISSN:1529-2908

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ni1229

    PubMed

  • Cell type-specific involvement of RIG-I in antiviral response. Reviewed

    Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S

    Immunity   23 ( 1 )   19 - 28   2005.07( ISSN:1074-7613

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.immuni.2005.04.010

    PubMed

  • B lymphocyte activation by human papillomavirus-like particles directly induces Ig class switch recombination via TLR4-MyD88. Reviewed

    Yang R, Murillo FM, Delannoy MJ, Blosser RL, Yutzy WH 4th, Uematsu S, Takeda K, Akira S, Viscidi RP, Roden RB

    Journal of immunology (Baltimore, Md. : 1950)   174 ( 12 )   7912 - 9   2005.06( ISSN:0022-1767

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    PubMed

  • Dendritic cell maturation induced by muramyl dipeptide (MDP) derivatives: monoacylated MDP confers TLR2/TLR4 activation. Reviewed

    Uehori J, Fukase K, Akazawa T, Uematsu S, Akira S, Funami K, Shingai M, Matsumoto M, Azuma I, Toyoshima K, Kusumoto S, Seya T

    Journal of immunology (Baltimore, Md. : 1950)   174 ( 11 )   7096 - 103   2005.06( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer. Reviewed

    Yang R, Wheeler CM, Chen X, Uematsu S, Takeda K, Akira S, Pastrana DV, Viscidi RP, Roden RB

    Journal of virology   79 ( 11 )   6741 - 50   2005.06( ISSN:0022-538X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/JVI.79.11.6741-6750.2005

    PubMed

  • Role of lipoteichoic acid in the phagocyte response to group B streptococcus. Reviewed

    Henneke P, Morath S, Uematsu S, Weichert S, Pfitzenmaier M, Takeuchi O, Müller A, Poyart C, Akira S, Berner R, Teti G, Geyer A, Hartung T, Trieu-Cuot P, Kasper DL, Golenbock DT

    Journal of immunology (Baltimore, Md. : 1950)   174 ( 10 )   6449 - 55   2005.05( ISSN:0022-1767

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    Publishing type:Research paper (scientific journal)  

    PubMed

  • Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction. Reviewed

    Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, Matsuda M, Coban C, Ishii KJ, Kawai T, Takeuchi O, Akira S

    The Journal of experimental medicine   201 ( 6 )   915 - 23   2005.03( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20042372

    PubMed

  • Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-beta. Reviewed

    Hirotani T, Yamamoto M, Kumagai Y, Uematsu S, Kawase I, Takeuchi O, Akira S

    Biochemical and biophysical research communications   328 ( 2 )   383 - 92   2005.03( ISSN:0006-291X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2004.12.184

    PubMed

  • Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. Reviewed

    Krishnegowda G, Hajjar AM, Zhu J, Douglass EJ, Uematsu S, Akira S, Woods AS, Gowda DC

    The Journal of biological chemistry   280 ( 9 )   8606 - 16   2005.03( ISSN:0021-9258

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M413541200

    PubMed

  • Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Reviewed

    Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, Endres S, Hartmann G

    Nature medicine   11 ( 3 )   263 - 70   2005.03( ISSN:1078-8956

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm1191

    PubMed

  • Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Reviewed

    Kumanogoh A, Shikina T, Suzuki K, Uematsu S, Yukawa K, Kashiwamura S, Tsutsui H, Yamamoto M, Takamatsu H, Ko-Mitamura EP, Takegahara N, Marukawa S, Ishida I, Morishita H, Prasad DV, Tamura M, Mizui M, Toyofuku T, Akira S, Takeda K, Okabe M, Kikutani H

    Immunity   22 ( 3 )   305 - 16   2005.03( ISSN:1074-7613

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.immuni.2005.01.014

    PubMed

  • [Role of toll-like receptor in immunological defence mechanism ]. Reviewed

    Uematsu S, Akira S

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   94 ( 2 )   355 - 61   2005.02( ISSN:0021-5384

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    PubMed

  • Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Reviewed

    Lang KS, Recher M, Junt T, Navarini AA, Harris NL, Freigang S, Odermatt B, Conrad C, Ittner LM, Bauer S, Luther SA, Uematsu S, Akira S, Hengartner H, Zinkernagel RM

    Nature medicine   11 ( 2 )   138 - 45   2005.02( ISSN:1078-8956

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm1176

    PubMed

  • Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. Reviewed

    Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, Yamamoto M, Takeuchi O, Itagaki S, Kumar N, Horii T, Akira S

    The Journal of experimental medicine   201 ( 1 )   19 - 25   2005.01( ISSN:0022-1007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20041836

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▼display all

Books and Other Publications

MISC

  • Characterization of the human gut virome in metabolic and autoimmune diseases(和訳中) Reviewed

    Fujimoto Kosuke, Miyaoka Daichi, Uematsu Satoshi

    Inflammation and Regeneration   42   1 of 6 - 6 of 6   2022.11( ISSN:1880-9693

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  • 【自己免疫疾患 層別化する新時代へ 臨床検体のマルチオミクス解析、腸内細菌によって見えてきた免疫経路の全容】(第1章)精密医療を目指したマルチオミクス解析によるアプローチ メタゲノム解析からの層別化医療への展望 Reviewed

    藤本 康介, 植松 智, 井元 清哉

    実験医学   40 ( 15 )   2374 - 2379   2022.09( ISSN:0288-5514

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    次世代シークエンサーによるゲノム解析技術の向上とともに、さまざまな疾患に関連する遺伝情報が明らかとなってきた。ヒトゲノムの情報だけでなく、さまざまなメタゲノムの情報が蓄積されてきたことで、メタゲノム解析を基盤とした新しい医療展開が強く期待されている。特に、ヒトマイクロバイオーム研究は近年ホットトピックスで、多くの研究者が腸内フローラに介入することで疾患を制御することをめざしている。本稿では、筆者らの研究グループが行った腸内細菌叢とウイルス叢のショットガンメタゲノム解析に基づくデータベースの構築、そして腸内細菌叢の遺伝子パスウェイ解析によって腸内細菌叢の「臓器」としての機能評価が可能となったことを概説する。さらに、メタゲノム解析を用いた今後の層別化医療の可能性について、特に疾患の発症や病態に直接的にかかわる病原常在腸内細菌(pathobiont)に注目した新規治療法の開発について紹介する。(著者抄録)

  • 【生活習慣と免疫異常】生活習慣病と病原常在腸内細菌 Reviewed

    藤本 康介, 植松 智

    臨床免疫・アレルギー科   77 ( 6 )   684 - 689   2022.06( ISSN:1881-1930

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  • 腸内細菌叢の異常を伴う疾患に対する新規治療法の開発 Reviewed

    植松 智

    日本毒性病理学会講演要旨集   38回   41 - 41   2022.01

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  • Clostridioides difficile感染症に対する新規制御法 Reviewed

    下吹越 正紀, 藤本 康介, 植松 智

    日本小児栄養消化器肝臓学会雑誌   35 ( 2 )   112 - 113   2021.12( ISSN:1346-9037

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  • 【ワクチン設計のサイエンス】自然免疫アジュバントを用いた新規粘膜ワクチン開発 Reviewed

    藤本 康介, 植松 智

    医学のあゆみ   279 ( 10 )   928 - 932   2021.12( ISSN:0039-2359

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    消化管をはじめとした粘膜面はさまざまな微生物にたえず曝されるため、外敵から身を守るためのユニークかつ効果的な粘膜免疫機構が存在する。その代表的なものとして、粘膜面には免疫グロブリンA(IgA)が多量に存在していることがあげられる。IgAの主な作用は、粘膜面に侵入してくる病原微生物の上皮細胞への付着・定義・侵入の阻止、病原微生物の産生する毒素や酵素に対する中和効果、粘液層での病原微生物の捕捉、抗菌作用などがあり、IgAは粘膜免疫防御機構を担う重要なプレーヤーである。したがって、病原微生物の標的となる粘膜面に高力価の病原微生物特異的なIgAを誘導することができれば、非常に効率のよい粘膜防御が可能となる。本稿では、標的となる粘膜面に高力価の抗原特異的IgAを誘導する作用をもつ自然免疫アジュバントを組み合わせた新規粘膜ワクチンについて、筆者らの最新の知見を含めて概説する。(著者抄録)

  • 【ワクチン設計のサイエンス】自然免疫アジュバントを用いた新規粘膜ワクチン開発 Reviewed

    藤本 康介, 植松 智

    医学のあゆみ   279 ( 10 )   928 - 932   2021.12( ISSN:0039-2359

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    消化管をはじめとした粘膜面はさまざまな微生物にたえず曝されるため、外敵から身を守るためのユニークかつ効果的な粘膜免疫機構が存在する。その代表的なものとして、粘膜面には免疫グロブリンA(IgA)が多量に存在していることがあげられる。IgAの主な作用は、粘膜面に侵入してくる病原微生物の上皮細胞への付着・定義・侵入の阻止、病原微生物の産生する毒素や酵素に対する中和効果、粘液層での病原微生物の捕捉、抗菌作用などがあり、IgAは粘膜免疫防御機構を担う重要なプレーヤーである。したがって、病原微生物の標的となる粘膜面に高力価の病原微生物特異的なIgAを誘導することができれば、非常に効率のよい粘膜防御が可能となる。本稿では、標的となる粘膜面に高力価の抗原特異的IgAを誘導する作用をもつ自然免疫アジュバントを組み合わせた新規粘膜ワクチンについて、筆者らの最新の知見を含めて概説する。(著者抄録)

    Other URL: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00060&link_issn=&doc_id=20211206010002&doc_link_id=issn%3D0039-2359%26volume%3D279%26issue%3D10%26spage%3D928&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D279%26issue%3D10%26spage%3D928&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • Mucosal vaccines against intestinal bacteria-mediated obesity Reviewed

    藤本康介, 藤本康介, 植松智, 植松智

    月刊メディカル・サイエンス・ダイジェスト   47 ( 11 )   592 - 593   2021.10( ISSN:1347-4340

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    J-GLOBAL

  • 糞便移植治療における腸内細菌叢と腸内ファージ叢の機能解析 Reviewed

    藤本 康介, 植松 智

    日本臨床免疫学会総会プログラム・抄録集   49回   73 - 73   2021.10

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  • 最先端医療の今 腸内細菌を標的としたヒト肥満ワクチンの開発研究 Reviewed

    藤本 康介, 植松 智

    Medical Science Digest   47 ( 11 )   592 - 593   2021.10( ISSN:1347-4340

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    ゲノム解析技術の進歩に伴い腸内細菌叢の構成異常(Dysbiosis)が肥満、糖尿病などのさまざまな疾患に影響を与えていることが明らかとなってきた。近年では糞便移植治療(腸内微生物移植治療)などを用いてDysbiosisの改善を目指すことで、病態の制御につなげようとする研究が世界中で進められている。本稿では、腸内細菌が介在する肥満の制御戦略について、新たに開発した粘膜ワクチン技術の視点から概説する。(著者抄録)

  • ファージゲノム解析に基づく腸内細菌叢制御の新戦略 Reviewed

    藤本 康介, 井元 清哉, 植松 智

    バイオサイエンスとインダストリー   79 ( 5 )   354 - 359   2021.09( ISSN:0914-8981

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    腸管内には常在微生物叢が存在し、宿主の健康に大きな影響を与えている。次世代シーケンサーを用いたゲノム解析技術の進展の結果、常在微生物叢の構成の乱れが様々な疾患の病態メカニズムに関係していることが明らかとなってきた。筆者らは、以前から腸内細菌を宿主とする腸内バクテリオファージ(ファージ)に着目し、腸内ファージゲノム解析パイプラインの確立やファージゲノムデータベースの構築を行ってきた。さらにはその解析技術を用いて、新たな腸内細菌制御法の開発に挑戦している。本稿では、ファージゲノムの解析手法の詳細や難治性疾患に対する腸内微生物叢の機能解析を概説しながら、筆者らの最新の知見を紹介する。(著者抄録)

    J-GLOBAL

  • 腸内細菌叢とがん 日本人健常者の腸内ファージと宿主細菌の感染ダイナミクス Reviewed

    植松 智

    日本癌学会総会記事   80回   [S12 - 4]   2021.09( ISSN:0546-0476

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  • ファージゲノム解析に基づく腸内細菌叢制御の新戦略 Reviewed

    藤本 康介, 井元 清哉, 植松 智

    バイオサイエンスとインダストリー   79 ( 5 )   354 - 359   2021.09( ISSN:0914-8981

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    腸管内には常在微生物叢が存在し、宿主の健康に大きな影響を与えている。次世代シーケンサーを用いたゲノム解析技術の進展の結果、常在微生物叢の構成の乱れが様々な疾患の病態メカニズムに関係していることが明らかとなってきた。筆者らは、以前から腸内細菌を宿主とする腸内バクテリオファージ(ファージ)に着目し、腸内ファージゲノム解析パイプラインの確立やファージゲノムデータベースの構築を行ってきた。さらにはその解析技術を用いて、新たな腸内細菌制御法の開発に挑戦している。本稿では、ファージゲノムの解析手法の詳細や難治性疾患に対する腸内微生物叢の機能解析を概説しながら、筆者らの最新の知見を紹介する。(著者抄録)

  • 腸内細菌叢の制御法の開発 Reviewed

    植松 智

    日本がん免疫学会総会プログラム・抄録集   25回   91 - 91   2021.05

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  • IgA誘導型新規粘膜ワクチン Reviewed

    藤本 康介, 植松 智

    臨床免疫・アレルギー科   75 ( 4 )   477 - 485   2021.04( ISSN:1881-1930

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  • IgA誘導型新規粘膜ワクチン Reviewed

    藤本 康介, 植松 智

    臨床免疫・アレルギー科   75 ( 4 )   477 - 485   2021.04( ISSN:1881-1930

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  • Clostridium ramosumを制御する新規粘膜ワクチンの臨床応用に向けた基剤開発 Reviewed

    藤井 厚一郎, 藤本 康介, 植松 智

    日本細菌学雑誌   76 ( 1 )   110 - 110   2021.02( ISSN:0021-4930 ( eISSN:1882-4110

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  • あなたの知らないファージの世界 ヒト腸内ウイルス叢解析を基盤とした腸内共生病原菌の制御法の開発 Reviewed

    藤本 康介, 植松 智

    日本細菌学雑誌   76 ( 1 )   42 - 42   2021.02( ISSN:0021-4930 ( eISSN:1882-4110

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  • 腸内ウイルスゲノムデータを用いた腸内細菌関連疾患に対する新たな治療戦略 Reviewed

    藤本 康介, 植松 智

    日本内科学会雑誌   110 ( Suppl. )   166 - 166   2021.02( ISSN:0021-5384 ( eISSN:1883-2083

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    J-GLOBAL

  • バクテリオファージ由来の新規酵素を用いたClostridioides difficile感染症の制御法の開発 Reviewed

    下吹越 正紀, 藤本 康介, 植松 智

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   123 - 123   2020.11

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    J-GLOBAL

  • Dysbiosis関連疾患に対する革新的な治療法の創出 Reviewed

    植松 智

    日本透析医学会雑誌   53 ( Suppl.1 )   247 - 247   2020.10( ISSN:1340-3451 ( eISSN:1883-082X

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    J-GLOBAL

  • ファージ由来の新規酵素を用いたClostridioides difficile感染症の制御 Reviewed

    下吹越 正紀, 藤本 康介, 植松 智

    日本臨床免疫学会総会プログラム・抄録集   48回   72 - 72   2020.10

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  • 病原常在腸内細菌を制御する新規粘膜ワクチンの臨床応用に向けた基剤開発 Reviewed

    川口 雄之亮, 藤本 康介, 植松 智

    日本臨床免疫学会総会プログラム・抄録集   48回   73 - 73   2020.10

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  • Development of prime-boost-type next-generation mucosal vaccines(和訳中) Reviewed

    Fujimoto Kosuke, Uematsu Satoshi

    Oxford University Press International Immunology   32 ( 9 )   597 - 603   2020.09( ISSN:0953-8178

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  • プライム-ブースト型次世代粘膜ワクチンの開発(Development of prime-boost-type next-generation mucosal vaccines) Reviewed

    Fujimoto Kosuke, Uematsu Satoshi

    International Immunology   32 ( 9 )   597 - 603   2020.09( ISSN:0953-8178

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  • Regulation of Clostridium ramosum-related disorders by mucosal vaccine Reviewed

    川口雄之亮, 藤本康介, 藤本康介, 齋藤武, 菱木知郎, 植松智, 植松智

    日本小児外科学会雑誌   56 ( 5 )   588 - 588   2020.09( ISSN:0288-609X ( eISSN:2187-4247

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    J-GLOBAL

  • 腸内細菌と肥満ワクチン Reviewed

    藤本 康介, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   73 ( 5 )   526 - 533   2020.05( ISSN:1881-1930

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  • Intestinal microbiota and mucosal vaccine for obesity. Reviewed

    藤本康介, 藤本康介, 植松智, 植松智

    月刊臨床免疫・アレルギー科   73 ( 5 )   526 - 533   2020.05( ISSN:1881-1930

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    J-GLOBAL

  • 腸内細菌と肥満ワクチン Reviewed

    藤本 康介, 植松 智

    臨床免疫・アレルギー科   73 ( 5 )   526 - 533   2020.05( ISSN:1881-1930

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  • 腸疾患と自然炎症 Reviewed

    佐藤 慎太郎, 植松 智, 清野 宏

    (株)先端医学社 炎症と免疫   28 ( 3 )   248 - 252   2020.04( ISSN:0918-8371

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    腸管は我々の体内に存在するが、体表面を覆う皮膚と同様、つねに外的環境に曝されている。そこには個体にとって「非自己」である腸内細菌叢も存在し、免疫担当細胞や抗菌ペプチドなどを産生する上皮細胞と協働しながら絶妙なバランスを保ち、腸内の恒常性を維持していると考えられている。何らかの原因でこのバランスが崩れると、一時的に、時には慢性的に、炎症反応が誘発され、炎症性腸疾患などのような自己免疫疾患の原因になり得ることがわかってきた。(著者抄録)

  • 腸疾患と自然炎症 Reviewed

    佐藤 慎太郎, 植松 智, 清野 宏

    炎症と免疫   28 ( 3 )   248 - 252   2020.04( ISSN:0918-8371 ( ISBN:9784865504613

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    腸管は我々の体内に存在するが、体表面を覆う皮膚と同様、つねに外的環境に曝されている。そこには個体にとって「非自己」である腸内細菌叢も存在し、免疫担当細胞や抗菌ペプチドなどを産生する上皮細胞と協働しながら絶妙なバランスを保ち、腸内の恒常性を維持していると考えられている。何らかの原因でこのバランスが崩れると、一時的に、時には慢性的に、炎症反応が誘発され、炎症性腸疾患などのような自己免疫疾患の原因になり得ることがわかってきた。(著者抄録)

    J-GLOBAL

  • 腸疾患と自然炎症 Reviewed

    佐藤 慎太郎, 植松 智, 清野 宏

    炎症と免疫   28 ( 3 )   248 - 252   2020.04( ISSN:0918-8371

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    腸管は我々の体内に存在するが、体表面を覆う皮膚と同様、つねに外的環境に曝されている。そこには個体にとって「非自己」である腸内細菌叢も存在し、免疫担当細胞や抗菌ペプチドなどを産生する上皮細胞と協働しながら絶妙なバランスを保ち、腸内の恒常性を維持していると考えられている。何らかの原因でこのバランスが崩れると、一時的に、時には慢性的に、炎症反応が誘発され、炎症性腸疾患などのような自己免疫疾患の原因になり得ることがわかってきた。(著者抄録)

  • 【生活習慣病と腸内細菌】糖尿病と腸内細菌 Reviewed

    藤本 康介, 植松 智

    (株)ライフ・サイエンス Progress in Medicine   40 ( 3 )   231 - 239   2020.03( ISSN:0287-3648

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  • 【生活習慣病と腸内細菌】糖尿病と腸内細菌 Reviewed

    藤本 康介, 植松 智

    Progress in Medicine   40 ( 3 )   231 - 239   2020.03( ISSN:0287-3648 ( ISBN:9784898016824

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    J-GLOBAL

  • 【生活習慣病と腸内細菌】糖尿病と腸内細菌 Reviewed

    藤本 康介, 植松 智

    Progress in Medicine   40 ( 3 )   231 - 239   2020.03( ISSN:0287-3648

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  • 抗原特異的な粘膜免疫応答を介した腸内細菌関連疾患の制御 Reviewed

    藤本 康介, 植松 智

    日本内科学会雑誌   109 ( Suppl. )   256 - 256   2020.02( ISSN:0021-5384 ( eISSN:1883-2083

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  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌が乱れる原因と体に及ぼす影響 Reviewed

    藤本 康介, 植松 智

    (株)メディカ出版 糖尿病ケア   17 ( 1 )   11 - 13   2020.01( ISSN:1348-9968

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  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌叢(腸内フローラ)とは Reviewed

    藤本 康介, 植松 智

    (株)メディカ出版 糖尿病ケア   17 ( 1 )   9 - 10   2020.01( ISSN:1348-9968

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  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌が乱れる原因と体に及ぼす影響 Reviewed

    藤本 康介, 植松 智

    糖尿病ケア   17 ( 1 )   11 - 13   2020.01( ISSN:1348-9968 ( ISBN:9784840470971

  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌叢(腸内フローラ)とは Reviewed

    藤本 康介, 植松 智

    糖尿病ケア   17 ( 1 )   9 - 10   2020.01( ISSN:1348-9968

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  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌が乱れる原因と体に及ぼす影響 Reviewed

    藤本 康介, 植松 智

    糖尿病ケア   17 ( 1 )   11 - 13   2020.01( ISSN:1348-9968

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  • 【スルスルわかる 糖尿病と腸内細菌の関係】腸内細菌の基本知識 腸内細菌叢(腸内フローラ)とは Reviewed

    藤本 康介, 植松 智

    糖尿病ケア   17 ( 1 )   9 - 10   2020.01( ISSN:1348-9968 ( ISBN:9784840470971

  • プライムブースト型次世代粘膜ワクチンの開発 Reviewed

    植松智, 植松智, 植松智

    日本ワクチン学会学術集会プログラム・抄録集   24th   2020

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    J-GLOBAL

  • 次世代シークエンサーを用いたヒト腸内フローラの経時的メタゲノム解析 Reviewed

    並河 由華, 藤本 康介, 植松 智, 岸本 英博

    琉球医学会誌   39 ( 1-4 )   104 - 104   2020( ISSN:1346-888X

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  • 次世代シークエンサーを用いたヒト腸内フローラの経時的メタゲノム解析 Reviewed

    並河 由華, 藤本 康介, 植松 智, 岸本 英博

    琉球医学会誌   39 ( 1-4 )   104 - 104   2020( ISSN:1346-888X

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  • 【好酸球が関与する難治病態と治療戦略】放射線腸障害に及ぼす好酸球の役割 Reviewed

    藤本 康介, 植松 智

    (株)北隆館 アレルギーの臨床   39 ( 14 )   1131 - 1134   2019.12( ISSN:0285-6379

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    腸管粘膜固有層には、樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在する。好酸球は腸管粘膜固有層に数多く存在するにも関わらず、その機能は未だ不明な点が多かった。好酸球が関連する消化管疾患としては、寄生虫感染症や難病に指定されている好酸球性消化管疾患(主に好酸球性食道炎と好酸球性胃腸炎に分類される)が良く知られている。さらに近年では、悪性腫瘍などの治療目的で放射線照射を受けた際に生じる放射線誘導性腸線維症の病態メカニズムに腸管粘膜固有層の好酸球がとても重要であることが明らかとなってきた。本稿では、筆者らの最新の知見を含めて概説する。(著者抄録)

  • 【好酸球が関与する難治病態と治療戦略】放射線腸障害に及ぼす好酸球の役割 Reviewed

    藤本 康介, 植松 智

    アレルギーの臨床   39 ( 14 )   1131 - 1134   2019.12( ISSN:0285-6379

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    腸管粘膜固有層には、樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在する。好酸球は腸管粘膜固有層に数多く存在するにも関わらず、その機能は未だ不明な点が多かった。好酸球が関連する消化管疾患としては、寄生虫感染症や難病に指定されている好酸球性消化管疾患(主に好酸球性食道炎と好酸球性胃腸炎に分類される)が良く知られている。さらに近年では、悪性腫瘍などの治療目的で放射線照射を受けた際に生じる放射線誘導性腸線維症の病態メカニズムに腸管粘膜固有層の好酸球がとても重要であることが明らかとなってきた。本稿では、筆者らの最新の知見を含めて概説する。(著者抄録)

    J-GLOBAL

  • 【好酸球が関与する難治病態と治療戦略】放射線腸障害に及ぼす好酸球の役割 Reviewed

    藤本 康介, 植松 智

    アレルギーの臨床   39 ( 14 )   1131 - 1134   2019.12( ISSN:0285-6379

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    腸管粘膜固有層には、樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在する。好酸球は腸管粘膜固有層に数多く存在するにも関わらず、その機能は未だ不明な点が多かった。好酸球が関連する消化管疾患としては、寄生虫感染症や難病に指定されている好酸球性消化管疾患(主に好酸球性食道炎と好酸球性胃腸炎に分類される)が良く知られている。さらに近年では、悪性腫瘍などの治療目的で放射線照射を受けた際に生じる放射線誘導性腸線維症の病態メカニズムに腸管粘膜固有層の好酸球がとても重要であることが明らかとなってきた。本稿では、筆者らの最新の知見を含めて概説する。(著者抄録)

  • 免疫疾患:消化器を症状にする疾患 新規粘膜ワクチンを用いた腸内細菌制御法の開発 Reviewed

    藤本 康介, 川口 雄之亮, 下吹越 正紀, 植松 智

    日本臨床免疫学会総会プログラム・抄録集   47回   77 - 77   2019.10

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    J-GLOBAL

  • 新規粘膜ワクチンを用いた肥満関連腸内細菌の制御 Reviewed

    藤本 康介, 川口 雄之亮, 下吹越 正紀, 植松 智

    日本臨床免疫学会総会プログラム・抄録集   47回   94 - 94   2019.10

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    J-GLOBAL

  • ゲノムワイド関連解析を用いた日本人腸内細菌叢の宿主遺伝要因の探索 Reviewed

    田中 正視, 石田 幸子, 加藤 久美子, 小田巻 俊孝, 密山 恵梨, 清水 金忠, 山口 類, 植松 智, 井元 清哉, 宮野 悟

    腸内細菌学雑誌   33 ( 2 )   114 - 114   2019.04( ISSN:1343-0882 ( eISSN:1349-8363

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    J-GLOBAL

  • 好酸球除去による放射線誘導性腸線維症の新規治療戦略 Reviewed

    植松 智

    (有)科学評論社 臨床免疫・アレルギー科   71 ( 1 )   71 - 77   2019.01( ISSN:1881-1930

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  • 好酸球除去による放射線誘導性腸線維症の新規治療戦略

    植松 智

    臨床免疫・アレルギー科   71 ( 1 )   71 - 77   2019.01( ISSN:1881-1930

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    J-GLOBAL

  • 好酸球除去による放射線誘導性腸線維症の新規治療戦略 Reviewed

    植松 智

    臨床免疫・アレルギー科   71 ( 1 )   71 - 77   2019.01( ISSN:1881-1930

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  • マウス脳由来ミクログリア細胞におけるヘモグロビン誘導膜結合型PGE<sub>2</sub>合成酵素の役割 Reviewed

    川端悠太, 柚木紀香, 加治美乃里, 植松智, 審良静男, 高橋達雄, 松尾由理

    日本薬学会北陸支部例会/日本病院薬剤師会北陸ブロック学術大会プログラム集&要旨集(Web)   131st-30th   2019

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  • リンパ学の明日を探る〜免疫学領域 好酸球と筋線維芽細胞の相互作用は、放射線誘導性腸線維症に必須の役割を果たす Reviewed

    植松 智

    日本リンパ学会 リンパ学   41 ( 2 )   92 - 95   2018.12( ISSN:0910-4186

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  • 腸管の自然免疫機構と疾患制御法の開発 Reviewed

    植松 智

    大阪市医学会 大阪市医学会雑誌   67   1 - 6   2018.12( ISSN:0386-4103

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    消化管は、侵入してくる病原微生物に対しては免疫応答を誘導して、適切に排除する。一方、食餌成分や常在細菌に対しては免疫寛容を誘導して過剰な免疫応答を起こさないようにしている。腸管粘膜固有層には、樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在し、腸管バリア機構の重要な役割を担っている。それらの免疫細胞は、自然免疫応答を通じて腸管免疫を制御していることが近年明らかとなってきた。例えば、腸管粘膜固有層の樹状細胞は、粘膜面の防御機構として非常に重要な免疫グロブリンA(immunoglobulin A;IgA)の誘導に重要であるだけでなく、Th1細胞やTh17細胞、制御性T細胞の誘導に重要である。一方、腸管粘膜固有層の好酸球は放射線障害によって誘導される腸管の繊維化の病態メカニズムにとても重要である。本稿では、筆者らの最新の知見を含めて概説する。(著者抄録)

  • リンパ学の明日を探る~免疫学領域 好酸球と筋線維芽細胞の相互作用は、放射線誘導性腸線維症に必須の役割を果たす Reviewed

    植松 智

    リンパ学   41 ( 2 )   92 - 95   2018.12( ISSN:0910-4186

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  • 腸管の自然免疫機構と疾患制御法の開発 Reviewed

    植松 智

    大阪市医学会雑誌   67   1 - 6   2018.12( ISSN:0386-4103

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    消化管は、侵入してくる病原微生物に対しては免疫応答を誘導して、適切に排除する。一方、食餌成分や常在細菌に対しては免疫寛容を誘導して過剰な免疫応答を起こさないようにしている。腸管粘膜固有層には、樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在し、腸管バリア機構の重要な役割を担っている。それらの免疫細胞は、自然免疫応答を通じて腸管免疫を制御していることが近年明らかとなってきた。例えば、腸管粘膜固有層の樹状細胞は、粘膜面の防御機構として非常に重要な免疫グロブリンA(immunoglobulin A;IgA)の誘導に重要であるだけでなく、Th1細胞やTh17細胞、制御性T細胞の誘導に重要である。一方、腸管粘膜固有層の好酸球は放射線障害によって誘導される腸管の繊維化の病態メカニズムにとても重要である。本稿では、筆者らの最新の知見を含めて概説する。(著者抄録)

  • 放射線誘導性腸線維症に対する好酸球除去を介した新規予防戦略 Reviewed

    武村 直紀, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   70 ( 2 )   168 - 174   2018.08( ISSN:1881-1930

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  • 放射線誘導性腸線維症に対する好酸球除去を介した新規予防戦略 Reviewed

    武村 直紀, 植松 智

    臨床免疫・アレルギー科   70 ( 2 )   168 - 174   2018.08( ISSN:1881-1930

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  • リンパ系を多面的に解く リンパ球と免疫 腸管樹状細胞と粘膜ワクチンの開発 Reviewed

    植松 智

    日本リンパ学会 リンパ学   41 ( 1 )   25 - 30   2018.06( ISSN:0910-4186

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  • 【自然免疫の最前線】 内因性リガンドによる自然免疫系の活性化 腸管バリア機構と自然免疫 Reviewed

    藤本 康介, 植松 智

    医歯薬出版(株) 医学のあゆみ   265 ( 13 )   1198 - 1203   2018.06( ISSN:0039-2359

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    食べ物や微生物との接触をたえず避けることのできない消化管は、宿主が危険にさらされる病原微生物に対しては適切に排除する一方で、食事成分など宿主が必要とするものに対しては過剰な免疫応答を起こさないという免疫寛容が備わっている。腸管粘膜固有層には樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在し、腸管バリア機構の一端を担っている。それらの免疫細胞は、自然免疫応答を通じて腸管免疫を制御していることが近年明らかとなってきた。たとえば、腸管粘膜固有層の樹状細胞は、粘膜面の防御機構として非常に重要な免疫グロブリンA(IgA)の誘導に重要であるだけでなく、Th1細胞やTh17細胞、制御性T細胞の誘導に重要である。一方、腸管粘膜固有層の好酸球は放射線障害によって誘導される腸管の線維化の病態メカニズムにとっても重要である。本稿では、著者らの最新の知見を含めて概説する。(著者抄録)

  • 好酸球を標的とした放射線誘導性腸線維症の新規治療戦略 Reviewed

    植松 智, 武村 直紀

    放射線生物研究会 放射線生物研究   53 ( 2 )   95 - 103   2018.06( ISSN:0441-747X

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    放射線誘導性腸線維症(Radiation-induced intestinal fibrosis;RIF)は、腹部の放射線治療後に見られる重篤な合併症である。その治療を目的として病因の解析を進めた。まず、マウス腹部への放射線照射は、小腸の粘膜下組織に好酸球を過剰に蓄積させてRIFを引き起すことを示した。一方、好酸球欠損マウスでは、放射線照射後のRIFは顕著に抑制されることから好酸球の寄与が示唆された。照射による慢性の陰窩細胞死は、細胞外アデノシン三リン酸の遊離を促し、粘膜下組織の筋線維芽細胞を活性化してC-Cモチーフケモカイン11(C-C motif chemokine ligand 11;CCL11)を発現させ、CCL11が好酸球を遊走させることが分かった。活性化筋線維芽細胞は、同時に顆粒球マクロファージコロニー刺激因子(granulocyte macrophage colony-stimulating factor;GM-CSF)も産生し、好酸球はGM-CSFで活性化されて、トランスフォーミング増殖因子(Transforming growth factor;TGF)-βを産生して、筋線維芽細胞による線維化を促進した。治療モデルとして、マウスの腸内好酸球をマウスIL-5受容体α抗体による処置により枯渇させたところ、RIFを非常に顕著かつ効果的に抑制された。以上のことから、我々は好酸球をRIFの病因として同定するのみならず、好酸球を標的とすることがRIFの新しい治療戦略となることを示した。(著者抄録)

  • 【自然免疫の最前線】内因性リガンドによる自然免疫系の活性化 腸管バリア機構と自然免疫 Reviewed

    藤本 康介, 植松 智

    医学のあゆみ   265 ( 13 )   1198 - 1203   2018.06( ISSN:0039-2359

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    食べ物や微生物との接触をたえず避けることのできない消化管は、宿主が危険にさらされる病原微生物に対しては適切に排除する一方で、食事成分など宿主が必要とするものに対しては過剰な免疫応答を起こさないという免疫寛容が備わっている。腸管粘膜固有層には樹状細胞やマクロファージ、好酸球といった自然免疫細胞が存在し、腸管バリア機構の一端を担っている。それらの免疫細胞は、自然免疫応答を通じて腸管免疫を制御していることが近年明らかとなってきた。たとえば、腸管粘膜固有層の樹状細胞は、粘膜面の防御機構として非常に重要な免疫グロブリンA(IgA)の誘導に重要であるだけでなく、Th1細胞やTh17細胞、制御性T細胞の誘導に重要である。一方、腸管粘膜固有層の好酸球は放射線障害によって誘導される腸管の線維化の病態メカニズムにとっても重要である。本稿では、著者らの最新の知見を含めて概説する。(著者抄録)

  • 好酸球を標的とした放射線誘導性腸線維症の新規治療戦略 Reviewed

    植松 智, 武村 直紀

    放射線生物研究   53 ( 2 )   95 - 103   2018.06( ISSN:0441-747X

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    放射線誘導性腸線維症(Radiation-induced intestinal fibrosis;RIF)は、腹部の放射線治療後に見られる重篤な合併症である。その治療を目的として病因の解析を進めた。まず、マウス腹部への放射線照射は、小腸の粘膜下組織に好酸球を過剰に蓄積させてRIFを引き起すことを示した。一方、好酸球欠損マウスでは、放射線照射後のRIFは顕著に抑制されることから好酸球の寄与が示唆された。照射による慢性の陰窩細胞死は、細胞外アデノシン三リン酸の遊離を促し、粘膜下組織の筋線維芽細胞を活性化してC-Cモチーフケモカイン11(C-C motif chemokine ligand 11;CCL11)を発現させ、CCL11が好酸球を遊走させることが分かった。活性化筋線維芽細胞は、同時に顆粒球マクロファージコロニー刺激因子(granulocyte macrophage colony-stimulating factor;GM-CSF)も産生し、好酸球はGM-CSFで活性化されて、トランスフォーミング増殖因子(Transforming growth factor;TGF)-βを産生して、筋線維芽細胞による線維化を促進した。治療モデルとして、マウスの腸内好酸球をマウスIL-5受容体α抗体による処置により枯渇させたところ、RIFを非常に顕著かつ効果的に抑制された。以上のことから、我々は好酸球をRIFの病因として同定するのみならず、好酸球を標的とすることがRIFの新しい治療戦略となることを示した。(著者抄録)

  • リンパ系を多面的に解く リンパ球と免疫 腸管樹状細胞と粘膜ワクチンの開発 Reviewed

    植松 智

    リンパ学   41 ( 1 )   25 - 30   2018.06( ISSN:0910-4186

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  • 【糖尿病と動脈硬化Update】 腸内細菌からみて Reviewed

    藤本 康介, 植松 智

    (有)フジメディカル出版 糖尿病の最新治療   9 ( 3 )   136 - 140   2018.05( ISSN:1884-2542

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    次世代シークエンサーの台頭により、ゲノム解析技術が飛躍的に向上した。それによって、さまざまな疾患に関連する遺伝的素因(ゲノムワイド関連解析による一塩基多型、single-nucleotide polymorphism:SNPなど)が精力的に解明されてきた。一方で、近年では疾患の発症や増悪に関わる環境因子として、腸内微生物叢が非常に注目されている。とくに、腸内細菌叢の構成異常(dysbiosis)は、炎症性腸疾患(クローン病や潰瘍性大腸炎)などの消化管疾患だけでなく、関節リウマチや多発性硬化症などの自己免疫疾患、さらには肥満、糖尿病、動脈硬化などの代謝性疾患にまで関連することが明らかになってきた。糖尿病や動脈硬化は患者数も多く、予防や治療の面からも非常に重要な疾患であるが、病態メカニズムについてはいまだ十分に解析されていない部分が多い。糖尿病や動脈硬化の病態を考えるうえで、腸内細菌叢と腸管免疫応答、さらに全身の免疫応答の相互作用は非常に重要である。(著者抄録)

  • 【糖尿病と動脈硬化Update】腸内細菌からみて Reviewed

    藤本 康介, 植松 智

    糖尿病の最新治療   9 ( 3 )   136 - 140   2018.05( ISSN:1884-2542

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    次世代シークエンサーの台頭により、ゲノム解析技術が飛躍的に向上した。それによって、さまざまな疾患に関連する遺伝的素因(ゲノムワイド関連解析による一塩基多型、single-nucleotide polymorphism:SNPなど)が精力的に解明されてきた。一方で、近年では疾患の発症や増悪に関わる環境因子として、腸内微生物叢が非常に注目されている。とくに、腸内細菌叢の構成異常(dysbiosis)は、炎症性腸疾患(クローン病や潰瘍性大腸炎)などの消化管疾患だけでなく、関節リウマチや多発性硬化症などの自己免疫疾患、さらには肥満、糖尿病、動脈硬化などの代謝性疾患にまで関連することが明らかになってきた。糖尿病や動脈硬化は患者数も多く、予防や治療の面からも非常に重要な疾患であるが、病態メカニズムについてはいまだ十分に解析されていない部分が多い。糖尿病や動脈硬化の病態を考えるうえで、腸内細菌叢と腸管免疫応答、さらに全身の免疫応答の相互作用は非常に重要である。(著者抄録)

  • 【近未来のワクチン-開発研究の潮流と課題】 ワクチン技術とサイエンスの新潮流 ワクチンアジュバントと粘膜ワクチンの基盤となる自然免疫細胞解析 Reviewed

    藤本 康介, 植松 智

    医歯薬出版(株) 医学のあゆみ   264 ( 5 )   397 - 402   2018.02( ISSN:0039-2359

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    さまざまな感染症を予防するためにワクチンは非常に重要であり、ワクチン開発によってこれまで私たちは重篤な感染症を克服してきた。ワクチン接種により免疫応答が誘導されるが、効率的な免疫応答がなければ有効な免疫記憶は成立しない。アルミニウム塩をはじめとしたアジュバントは自然免疫を活性化させる物質で、ワクチンにとって必要不可欠なものである。近年では、従来の注射型ワクチンだけでなく、次世代ワクチンとして粘膜ワクチンが注目されている。粘膜ワクチンは、全身性の免疫応答のみならず、粘膜局所での免疫応答も誘導することから、効率的な感染防御応答を誘導できるため、感染症に対する有効なワクチンと考えられている。さらに、免疫グロブリンA(IgA)は粘膜免疫応答にとって重要な役割を担っており、その誘導機構が明らかとなってきた。本稿では、著者らの知見を含めて概説する。(著者抄録)

  • 【近未来のワクチン-開発研究の潮流と課題】ワクチン技術とサイエンスの新潮流 ワクチンアジュバントと粘膜ワクチンの基盤となる自然免疫細胞解析 Reviewed

    藤本 康介, 植松 智

    医学のあゆみ   264 ( 5 )   397 - 402   2018.02( ISSN:0039-2359

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    さまざまな感染症を予防するためにワクチンは非常に重要であり、ワクチン開発によってこれまで私たちは重篤な感染症を克服してきた。ワクチン接種により免疫応答が誘導されるが、効率的な免疫応答がなければ有効な免疫記憶は成立しない。アルミニウム塩をはじめとしたアジュバントは自然免疫を活性化させる物質で、ワクチンにとって必要不可欠なものである。近年では、従来の注射型ワクチンだけでなく、次世代ワクチンとして粘膜ワクチンが注目されている。粘膜ワクチンは、全身性の免疫応答のみならず、粘膜局所での免疫応答も誘導することから、効率的な感染防御応答を誘導できるため、感染症に対する有効なワクチンと考えられている。さらに、免疫グロブリンA(IgA)は粘膜免疫応答にとって重要な役割を担っており、その誘導機構が明らかとなってきた。本稿では、著者らの知見を含めて概説する。(著者抄録)

  • 免疫学 腸内真菌叢の解析 Reviewed

    藤本 康介, 植松 智

    医歯薬出版(株) 医学のあゆみ   264 ( 2 )   180 - 181   2018.01( ISSN:0039-2359

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  • 免疫学 腸内真菌叢の解析 Reviewed

    藤本 康介, 植松 智

    医学のあゆみ   264 ( 2 )   180 - 181   2018.01( ISSN:0039-2359

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  • Innovative prime-boost vaccine method strongly induces both systemic and mucosal immunity Reviewed

    Kosuke Fujimoto, Naoki Takemura, Satoshi Uematsu

    ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD CYTOKINE   100   174 - 175   2017.12( ISSN:1043-4666

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  • 【生体バリア 粘膜や皮膚を舞台とした健康と疾患のダイナミクス】 (第2章)臓器特異的バリアとその破綻による疾患 消化管バリアと疾患 放射線性消化管症候群 放射線による腸上皮バリア破壊における自然免疫の役割 Reviewed

    武村 直紀, 植松 智

    (株)羊土社 実験医学   35 ( 7 )   1163 - 1168   2017.05( ISSN:0288-5514

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    われわれの身体は皮膚や粘膜を介して外界と接しており、その表面には異物の侵入を阻止するために上皮バリアが形成されている。消化管は最も広大な面積をもつ粘膜組織で、口から入る食物や微生物、さらには腸内細菌に日頃から曝されており、上皮バリアの破綻は敗血症や腸炎などの重篤な病状へと直結する。放射線は消化管の上皮バリアを著しく傷害する危険性を秘めており、がん治療などでそれに関連した障害が発生する(消化管症候群)。本稿では、消化管症候群に関する従来の理解とともに、自然免疫がその予防のための新たな標的となる可能性について概説する。(著者抄録)

  • 【生体バリア 粘膜や皮膚を舞台とした健康と疾患のダイナミクス】(第2章)臓器特異的バリアとその破綻による疾患 消化管バリアと疾患 放射線性消化管症候群 放射線による腸上皮バリア破壊における自然免疫の役割 Reviewed

    武村 直紀, 植松 智

    実験医学   35 ( 7 )   1163 - 1168   2017.05( ISSN:0288-5514

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    われわれの身体は皮膚や粘膜を介して外界と接しており、その表面には異物の侵入を阻止するために上皮バリアが形成されている。消化管は最も広大な面積をもつ粘膜組織で、口から入る食物や微生物、さらには腸内細菌に日頃から曝されており、上皮バリアの破綻は敗血症や腸炎などの重篤な病状へと直結する。放射線は消化管の上皮バリアを著しく傷害する危険性を秘めており、がん治療などでそれに関連した障害が発生する(消化管症候群)。本稿では、消化管症候群に関する従来の理解とともに、自然免疫がその予防のための新たな標的となる可能性について概説する。(著者抄録)

  • 放射線による腸上皮バリア破壊における自然免疫の役割 Reviewed

    武村 直紀, 植松 智

    実験医学増刊号   35 ( 7 )   121 - 126   2017.04

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  • 慢性炎症におけるリンパの役割 小腸の急性放射線腸障害におけるTLR3の役割 Reviewed

    植松 智

    日本リンパ学会 リンパ学   39 ( 2 )   101 - 104   2016.12( ISSN:0910-4186

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  • 慢性炎症におけるリンパの役割 小腸の急性放射線腸障害におけるTLR3の役割 Reviewed

    植松 智

    リンパ学   39 ( 2 )   101 - 104   2016.12( ISSN:0910-4186

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  • Toll様受容体を標的とした急性放射線性消化管症候群の新たな予防戦略 Reviewed

    武村 直紀, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   66 ( 3 )   267 - 273   2016.09( ISSN:1881-1930

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  • Toll様受容体を標的とした急性放射線性消化管症候群の新たな予防戦略 Reviewed

    武村 直紀, 植松 智

    臨床免疫・アレルギー科   66 ( 3 )   267 - 273   2016.09( ISSN:1881-1930

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  • 消化管自然免疫からみた食物アレルギーの成立機構 Reviewed

    植松 智

    日本職業・環境アレルギー学会 日本職業・環境アレルギー学会雑誌   23 ( 2 )   9 - 14   2016.05( ISSN:1349-5461

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    免疫系は病原体分子を異物として認識し、防御反応を誘導する。ところが、環境や個人の体質によっては、本来は無害な分子に対して獲得免疫が誘導され、炎症や組織障害が起こる。無害な環境抗原に対する免疫系の過剰反応を「アレルギー反応」といい、それを惹起する環境抗原をアレルゲンという。食物アレルギーは、原因物質を摂取した後に生じるアレルギー応答である。時にアナフィラキシーショックを誘導する。IgE依存性の一般的な食物アレルギーとIgE非依存性アレルギー(グルテン不耐症のセリアック病など)に分類される。IgE依存性の食物アレルギーは、I型(即時型)とTh2細胞を主体とするIV型(遅延型)応答による複合病態である。アレルギーの分子メカニズムの解明に伴い、新しい治療法の開発が試みられている。(著者抄録)

  • 【細胞死 新しい実行メカニズムの謎に迫り疾患を理解する ネクロプトーシス、パイロトーシス、フェロトーシスとは?死を契機に引き起こされる免疫、炎症、再生の分子機構とは?】 (第2章)死細胞の認識、貪食、生体応答 放射線誘導性細胞死が引き起こす臓器障害に対する自然免疫学的治療戦略 Reviewed

    武村 直紀, 植松 智

    (株)羊土社 実験医学   34 ( 7 )   1118 - 1123   2016.05( ISSN:0288-5514

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    われわれの細胞が放射線に曝されてDNAに傷害を受けると細胞死が誘導され、その影響がひいては放射線障害とよばれるさまざまな臓器機能障害を招来する。これまでに、放射線誘導性細胞死の分子機構は細緻に至るまで解明されているものの、その応答は傷害を受けた細胞のがん化を防ぐための重要な機能と考えられることから、その意義を損なうことなく組織の細胞を保存できる手段が求められていた。本稿では、自然免疫機能の活性化を制御することで放射線障害を抑制できるという全く新たな戦略を示唆する最近の研究について概括する。(著者抄録)

  • 【細胞死 新しい実行メカニズムの謎に迫り疾患を理解する ネクロプトーシス、パイロトーシス、フェロトーシスとは?死を契機に引き起こされる免疫、炎症、再生の分子機構とは?】(第2章)死細胞の認識、貪食、生体応答 放射線誘導性細胞死が引き起こす臓器障害に対する自然免疫学的治療戦略 Reviewed

    武村 直紀, 植松 智

    実験医学   34 ( 7 )   1118 - 1123   2016.05( ISSN:0288-5514

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    われわれの細胞が放射線に曝されてDNAに傷害を受けると細胞死が誘導され、その影響がひいては放射線障害とよばれるさまざまな臓器機能障害を招来する。これまでに、放射線誘導性細胞死の分子機構は細緻に至るまで解明されているものの、その応答は傷害を受けた細胞のがん化を防ぐための重要な機能と考えられることから、その意義を損なうことなく組織の細胞を保存できる手段が求められていた。本稿では、自然免疫機能の活性化を制御することで放射線障害を抑制できるという全く新たな戦略を示唆する最近の研究について概括する。(著者抄録)

  • 消化管自然免疫からみた食物アレルギーの成立機構 Reviewed

    植松 智

    日本職業・環境アレルギー学会雑誌   23 ( 2 )   9 - 14   2016.05( ISSN:1349-5461

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    免疫系は病原体分子を異物として認識し、防御反応を誘導する。ところが、環境や個人の体質によっては、本来は無害な分子に対して獲得免疫が誘導され、炎症や組織障害が起こる。無害な環境抗原に対する免疫系の過剰反応を「アレルギー反応」といい、それを惹起する環境抗原をアレルゲンという。食物アレルギーは、原因物質を摂取した後に生じるアレルギー応答である。時にアナフィラキシーショックを誘導する。IgE依存性の一般的な食物アレルギーとIgE非依存性アレルギー(グルテン不耐症のセリアック病など)に分類される。IgE依存性の食物アレルギーは、I型(即時型)とTh2細胞を主体とするIV型(遅延型)応答による複合病態である。アレルギーの分子メカニズムの解明に伴い、新しい治療法の開発が試みられている。(著者抄録)

  • 放射線誘導性細胞死が引き起こす臓器障害に対する自然免疫学的治療戦略 Reviewed

    武村 直紀, 植松 智

    実験医学増刊号   34 ( 7 )   110 - 115   2016.04

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  • 【自然免疫による炎症制御機構】 放射線誘導性腸管上皮傷害におけるTLR3の役割 Reviewed

    武村 直紀, 植松 智

    (株)先端医学社 炎症と免疫   24 ( 1 )   10 - 16   2015.12( ISSN:0918-8371

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    放射線事故あるいは放射線治療において消化管が高線量の放射線に曝されると、急性放射線性消化管症候群とよばれる重篤な障害が起きる。その病態機構について、これまでの研究によって多くの知見が得られてはいるものの、有効な予防・治療手段は確立されていない。Toll様受容体は代表的な自然免疫受容体の一つであり、感染防御において重要な免疫応答を誘導する。ところが近年では、本来の防御機能とは裏腹に、特定の疾患においてはTLRによる炎症応答が組織傷害を増悪させていることが明らかとなりつつある。本稿では、急性放射線性消化管症候群の成立にTLR3がきわめて重要な役割を果たしており、その阻害が有効な予防・治療法となりうることについて紹介する。(著者抄録)

  • 【自然免疫による炎症制御機構】放射線誘導性腸管上皮傷害におけるTLR3の役割 Reviewed

    武村 直紀, 植松 智

    炎症と免疫   24 ( 1 )   10 - 16   2015.12( ISSN:0918-8371

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    放射線事故あるいは放射線治療において消化管が高線量の放射線に曝されると、急性放射線性消化管症候群とよばれる重篤な障害が起きる。その病態機構について、これまでの研究によって多くの知見が得られてはいるものの、有効な予防・治療手段は確立されていない。Toll様受容体は代表的な自然免疫受容体の一つであり、感染防御において重要な免疫応答を誘導する。ところが近年では、本来の防御機能とは裏腹に、特定の疾患においてはTLRによる炎症応答が組織傷害を増悪させていることが明らかとなりつつある。本稿では、急性放射線性消化管症候群の成立にTLR3がきわめて重要な役割を果たしており、その阻害が有効な予防・治療法となりうることについて紹介する。(著者抄録)

  • 【腸管免疫の制御】 小腸粘膜固有層の自然免疫細胞が担う腸管免疫応答 Reviewed

    武村 直紀, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   64 ( 4 )   318 - 325   2015.10( ISSN:1881-1930

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  • 【腸管免疫の制御】小腸粘膜固有層の自然免疫細胞が担う腸管免疫応答 Reviewed

    武村 直紀, 植松 智

    臨床免疫・アレルギー科   64 ( 4 )   318 - 325   2015.10( ISSN:1881-1930

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  • 放射線誘導性小腸上皮傷害におけるTLR3の役割 Reviewed

    武村 直紀, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   64 ( 1 )   70 - 77   2015.07( ISSN:1881-1930

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  • 粘膜関連リンパ組織形成における最新知見 Reviewed

    植松 智, 清野 宏

    日本リンパ学会 リンパ学   38 ( 1 )   27 - 29   2015.07( ISSN:0910-4186

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  • 放射線誘導性小腸上皮傷害におけるTLR3の役割 Reviewed

    武村 直紀, 植松 智

    臨床免疫・アレルギー科   64 ( 1 )   70 - 77   2015.07( ISSN:1881-1930

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  • 粘膜関連リンパ組織形成における最新知見 Reviewed

    植松 智, 清野 宏

    リンパ学   38 ( 1 )   27 - 29   2015.07( ISSN:0910-4186

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  • 【粘膜免疫Update】 基礎 Toll様受容体と急性放射線性消化管症候群 Reviewed

    武村 直紀, 植松 智

    医歯薬出版(株) 医学のあゆみ   253 ( 5 )   403 - 409   2015.05( ISSN:0039-2359

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    電離放射線に被曝した臓器は、その感受性に応じてさまざまな機能障害を起こす。急性放射線性消化管症候群は、放射線事故あるいは癌の放射線治療において消化管が高線量の放射線に曝された場合に引き起こされる重篤な障害である。その病態機構についてヒトや動物で数多くの研究がなされているにもかかわらず、有効な予防・治療手段はいまだに確立されていない。Toll様受容体(TLR)は代表的な自然免疫受容体のひとつであり、病原体に対する感染防御において重要な免疫応答を惹起することで知られている。ところが近年では、本来の防御機能とは裏腹に、特定の炎症性疾患や自己免疫疾患においてはTLRによって誘導された応答が組織傷害を増悪させていることが明らかとなりつつあり、あらたな治療標的としての認識が高まっている。本稿では急性放射線性消化管症候群に関する理解についての最近の進歩とともに、その病態形成機構へのTLRの関与について概括する。(著者抄録)

  • 【粘膜免疫Update】基礎 Toll様受容体と急性放射線性消化管症候群 Reviewed

    武村 直紀, 植松 智

    医学のあゆみ   253 ( 5 )   403 - 409   2015.05( ISSN:0039-2359

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    電離放射線に被曝した臓器は、その感受性に応じてさまざまな機能障害を起こす。急性放射線性消化管症候群は、放射線事故あるいは癌の放射線治療において消化管が高線量の放射線に曝された場合に引き起こされる重篤な障害である。その病態機構についてヒトや動物で数多くの研究がなされているにもかかわらず、有効な予防・治療手段はいまだに確立されていない。Toll様受容体(TLR)は代表的な自然免疫受容体のひとつであり、病原体に対する感染防御において重要な免疫応答を惹起することで知られている。ところが近年では、本来の防御機能とは裏腹に、特定の炎症性疾患や自己免疫疾患においてはTLRによって誘導された応答が組織傷害を増悪させていることが明らかとなりつつあり、あらたな治療標的としての認識が高まっている。本稿では急性放射線性消化管症候群に関する理解についての最近の進歩とともに、その病態形成機構へのTLRの関与について概括する。(著者抄録)

  • 急性放射線性消化管症候群におけるToll様受容体の役割 Reviewed

    武村 直紀, 植松 智

    放射線生物研究会 放射線生物研究   50 ( 1 )   84 - 97   2015.03( ISSN:0441-747X

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    電離放射線は被曝臓器の感受性に応じて様々な障害を引き起こす。急性放射線性消化管症候群は放射線事故あるいは癌の放射線治療において、消化管が高線量の放射線に被曝した場合に引き起こされる重篤な障害である。その病態機構について、ヒトや動物で数多くの研究がなされているにもかかわらず、有効な治療手段は未だに確立されていない。Toll様受容体(TLR)は最も代表的な自然免疫受容体の一つであり、病原体の感染防御に対して重要な免疫応答を惹起することで知られている。ところが近年の報告によると、本来の防御機能とは対照的に、TLRによって誘導された応答が特定の炎症性疾患や自己免疫疾患において組織傷害を増悪させていることが明らかとなりつつある。今回の総説では、急性放射線性消化管症候群に関する理解についての最近の進歩とともに、その病態形成機構へのTLRの寄与について概括する。(著者抄録)

  • 急性放射線性消化管症候群におけるToll様受容体の役割 Reviewed

    武村 直紀, 植松 智

    放射線生物研究   50 ( 1 )   84 - 97   2015.03( ISSN:0441-747X

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    電離放射線は被曝臓器の感受性に応じて様々な障害を引き起こす。急性放射線性消化管症候群は放射線事故あるいは癌の放射線治療において、消化管が高線量の放射線に被曝した場合に引き起こされる重篤な障害である。その病態機構について、ヒトや動物で数多くの研究がなされているにもかかわらず、有効な治療手段は未だに確立されていない。Toll様受容体(TLR)は最も代表的な自然免疫受容体の一つであり、病原体の感染防御に対して重要な免疫応答を惹起することで知られている。ところが近年の報告によると、本来の防御機能とは対照的に、TLRによって誘導された応答が特定の炎症性疾患や自己免疫疾患において組織傷害を増悪させていることが明らかとなりつつある。今回の総説では、急性放射線性消化管症候群に関する理解についての最近の進歩とともに、その病態形成機構へのTLRの寄与について概括する。(著者抄録)

  • 【樹状細胞とリンパ球の活性化】 小腸粘膜固有層の樹状細胞によるTh細胞応答の制御 Reviewed

    武村 直紀, 植松 智

    (有)科学評論社 臨床免疫・アレルギー科   58 ( 5 )   508 - 516   2012.11( ISSN:1881-1930

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  • 【樹状細胞とリンパ球の活性化】小腸粘膜固有層の樹状細胞によるTh細胞応答の制御 Reviewed

    武村 直紀, 植松 智

    臨床免疫・アレルギー科   58 ( 5 )   508 - 516   2012.11( ISSN:1881-1930

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • What's New in SURGERY FRONTIER(第71回) 粘膜の監視・排除・共生システム 小腸樹状細胞の新たな分類と免疫機構 Reviewed

    藤本 康介, 植松 智

    (株)メディカルレビュー社 Surgery Frontier   18 ( 4 )   394 - 397   2011.12( ISSN:1340-5594

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  • What's New in SURGERY FRONTIER(第71回) 粘膜の監視・排除・共生システム 小腸樹状細胞の新たな分類と免疫機構 Reviewed

    藤本 康介, 植松 智

    Surgery Frontier   18 ( 4 )   394 - 397   2011.12( ISSN:1340-5594

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  • 【粘膜免疫システム 分子レベルで明らかになってきた監視・排除・共生機構と腸内細菌の全貌】 腸内細菌に対する粘膜防御機構における小腸樹状細胞の役割 Reviewed

    武村 直紀, 植松 智

    (株)学研メディカル秀潤社 細胞工学   30 ( 4 )   353 - 360   2011.03( ISSN:0287-3796

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 【粘膜免疫システム 分子レベルで明らかになってきた監視・排除・共生機構と腸内細菌の全貌】腸内細菌に対する粘膜防御機構における小腸樹状細胞の役割 Reviewed

    武村 直紀, 植松 智

    細胞工学   30 ( 4 )   353 - 360   2011.03( ISSN:0287-3796

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  • 腸管の自然免疫系(The innate immune system in the intestine) Reviewed

    Uematsu Satoshi, Fujimoto Kosuke

    John Wiley & Sons Australia, Ltd Microbiology and Immunology   54 ( 11 )   645 - 657   2010.11( ISSN:0385-5600

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  • 腸管の自然免疫系(The innate immune system in the intestine) Reviewed

    Uematsu Satoshi, Fujimoto Kosuke

    Microbiology and Immunology   54 ( 11 )   645 - 657   2010.11( ISSN:0385-5600

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  • 臨床医が知っておきたい自然免疫の知識 基本から最新知見まで Reviewed

    植松 智

    (一社)大阪小児科医会 大阪小児科医会会報   ( 152 )   19 - 26   2010.01( ISSN:2189-4736

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Kind of work:Single Work  

  • 臨床医が知っておきたい自然免疫の知識 基本から最新知見まで Reviewed

    植松 智

    大阪小児科医会会報   ( 152 )   19 - 26   2010.01( ISSN:2189-4736

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Presentations

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Industrial Property Rights

  • 放射線障害の治療又は予防剤並びに治療又は予防方法

    岡田 和樹, 森 聖寿, 植松 智, 武村 直紀

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    property_type:Patent 

    Application no:特願2022-195156 

    Announcement no:特開2023-025212 

    J-GLOBAL

  • ワクチン用アジュバント、ワクチン、及び免疫誘導方法

    植松 智, 武村 直紀

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    property_type:Patent 

    Application no:特願2017-523721 

    Patent/Registration no:特許第6534146号 

    J-GLOBAL

  • ワクチン用アジュバント、ワクチン、及び免疫誘導方法

    植松 智, 武村 直紀

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    property_type:Patent 

    Application no:JP2016067403 

    Announcement no:WO2016-199904 

    Publication no:WO2016-199904 

    Patent/Registration no:特許第6534146号 

    J-GLOBAL

Grant-in-Aid for Scientific Research

  • 腸内pathobiontを標的としたファージ療法開発のための基盤研究

    Grant-in-Aid for Scientific Research(A)  2022.04

  • 疾患メタゲノム解析による腸内微生物叢の臓器機能評価のための情報基盤技術の開発

    Grant-in-Aid for Scientific Research(B)  2021.04

  • 腸内pathobiontを標的としたファージ療法開発のための基盤研究

    Grant-in-Aid for Scientific Research(A)  2023.04

  • 疾患メタゲノム解析による腸内微生物叢の臓器機能評価のための情報基盤技術の開発

    Grant-in-Aid for Scientific Research(B)  2023.04

  • がん転移における免疫チェックポイントの制御とプロスタグランジンEの役割

    Grant-in-Aid for Scientific Research(B)  2018.04

  • Development study of next generation mucosal vaccine by dendritic cell modification

    Grant-in-Aid for Challenging Research (Pioneering)/(Exploratory)  2017.06

  • 自然免疫機構を標的とした新規放射線性消化管症候群の治療法の開発

    Grant-in-Aid for Scientific Research(B)  2017.04

  • Development of antigen specific immune cell therapy based on Crispr/Cas9 genome editing system

    Grant-in-Aid for Challenging Research (Pioneering)/(Exploratory)  2015.04

  • Development of a novel method for therapy against autoimmune disease

    Grant-in-Aid for Scientific Research(C)  2015.04

  • 急性、慢性放射線腸障害におけるダイイングコードの解明

    新学術領域研究(研究領域提案型)  2015.04

  • Analysis of innate immune cells in small intestinal lamina propria

    Grant-in-Aid for Scientific Research(C)  2012.04

  • The analysis of antigen presenting cells in mouse and human intestinal lamina propria

    Grant-in-Aid for Young Scientists(A)  2009

  • 腸管粘膜固有層のTLR5発現樹状細胞による細菌感染防御機構

    Grant-in-Aid for Scientific Research on Priority Areas  2009

  • Analysis of transcriptional activation and isoforms of NF-IL6 in innate immunity

    Grant-in-Aid for Young Scientists(B)  2007

  • マウスのサルモネラ腸炎モデルを用いたTLR5の機能解析

    Grant-in-Aid for Young Scientists(B)  2005

  • NF-IL6の転写活性化様式とそのアイソフォームの機能解析

    Grant-in-Aid for JSPS Fellows  2003

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Contract research

  • 腸内マイクロバイオーム制御による次世代創薬技術の開発/課題2:MBデジタルツイン技術を基盤とした腸管免疫関連疾患の制御法の開発

    国立研究開発法人 日本医療研究開発機構  次世代治療・診断実現のための創薬基盤技術開発事業(腸内マイクロバイオーム制御による次世代創薬技術の開発)  2023

  • 網羅的メタゲノム解析を基盤とした革新的なファージ療法の開発

    国立研究開発法人 日本医療研究開発機構  新興・再興感染症に対する革新的医薬品等開発推進研究事業  2023

Outline of education staff

  • 免疫系コースでは、感染が起こってから自然免疫が発動し、獲得免疫が誘導される基本的な免疫応答を軸として、免疫現象全体を細胞レベル、分子レベルで理解を図る。前半では、総論として免疫細胞の分化と機能、エフェクター分子と機構、自然免疫受容体の機能、抗原提示、獲得免疫の多様性の獲得と誘導、エフェクター細胞の機能、さらに粘膜免疫機構、免疫制御機構、免疫記憶を詳細に学ぶ。また、機能細胞形態学の宇留島先生との連携のもと、免疫応答が起こる場として免疫関連組織、臓器の学びを行い、水平講義を展開し免疫応答の時空間的な理解を深める。後半では、総論で学んだ生理的、正常状態での免疫応答に関する基礎知識を基盤として、炎症、アレルギー、癌、免疫不全といった免疫疾患の病態機構を一緒に考えつつ、治療法も含めた学びを深めていく。さらに、膠原病内科学の橋本先生との連携の元、基礎と臨床の橋渡しとなる膠原病の講義を展開し、病態機構、治療、さらには最先端の分子標的薬の紹介も含めた垂直講義を実践する。最後の授業では、再度、感染が起こってから自然免疫が発動し、獲得免疫が誘導される免疫応答に関して、コース全体のダイジェスト、総まとめの講義を行い、各回の要点をピンチアウトしながら、全体を理解しつつも細部との連関をきっちりと再確認してもらう。

Charge of on-campus class subject

  • Immunology

    2020   Intensive lecture   Undergraduate

  • 免疫系コース

    2021   Intensive lecture   Undergraduate

  • 免疫系コース

    2022   Intensive lecture   Undergraduate

  • 免疫系コース

    2023   Intensive lecture   Undergraduate

  • 初年次ゼミナール

    2023   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in metagenomics)

    2023   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in mucosal immunity)

    2023   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in innate immunity)

    2023   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in immunology)

    2023   Weekly class   Graduate school

  • 老年医科学演習(ゲノム免疫学)

    2023   Weekly class   Graduate school

  • 老年医科学(ゲノム免疫学)

    2023   Weekly class   Graduate school

  • 人体を考える

    2022   Weekly class   Undergraduate

  • 老年医科学(ゲノム免疫学)

    2022   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in metagenomics)

    2022   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in mucosal immunity)

    2022   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in innate immunity)

    2022   Weekly class   Graduate school

  • Immunology and Genomics(Seminar in immunology)

    2022   Weekly class   Graduate school

  • 老年医科学演習(ゲノム免疫学)

    2022   Weekly class   Graduate school

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Charge of off-campus class subject

  • 免疫学

    2020.04
    -
    2022.03

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    Level:Undergraduate (specialized) 

  • 免疫学

    2014.06
    -
    2018.08

  • 病理学

    2005.04
    -
    2022.03
    Institution:Hyogo College of Medicine

  • 免疫学

    Institution:University of Occupational and Environmental Health, Japan

Faculty development activities

  • FD講習会  2023

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    FD講習会で講師を行った

Number of papers published by graduate students

  • 2023

    Number of undergraduate student / college student presentations:Number of graduate students presentations:1

  • 2021

    Number of undergraduate student / college student presentations:Number of graduate students presentations:1

  • 2020

    Number of undergraduate student / college student presentations:Number of graduate students presentations:1

  • 2019

    Number of undergraduate student / college student presentations:Number of graduate students presentations:1

Number of instructed thesis, researches

  • 2023

    Number of instructed the graduation thesis:Number of graduation thesis reviews:2

    [Number of instructed the Master's Program] (previous term):

    [Number of doctoral thesis reviews] (chief):[Number of doctoral thesis reviews] (vice-chief):2

Media Coverage

  • ニキビ治療に「ファージ療法」 Newspaper, magazine

    読売新聞  2024.01

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    SDGs:

  • ニキビ治療に「ファージ療法」、特定の細菌に感染して破壊…大阪公立大が国内初の臨床研究へ Internet

    Yahoo!ニュース  2024.01

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  • ニキビ治療に「ファージ療法」、特定の細菌に感染して破壊…大阪公立大が国内初の臨床研究へ Internet

    読売新聞オンライン yomiDr.  2024.01

  • 尋常性ざ瘡(ニキビ)に対するバクテリオファージ療法、臨床試験開始-大阪公立大 Internet

    医療NEWS QLife Pro  2024.01

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    Pharmacy Times  2023.12

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    Medindia  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    News-Medical  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    Asia Research News  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    Alpha Galileo  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    EurekAlert!  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    Medical Xpress  2023.11

  • Prime-boost-type PspA3+2 Mucosal Vaccine Protects Cynomolgus Macaques from Intratracheal Challenge with Pneumococci Internet

    ScienceDaily  2023.11

  • プライム-ブースト型粘膜ワクチンの開発 Internet

    奉優会ニュース  2023.11

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  • プライム-ブースト型粘膜ワクチンの開発 Internet

    文教速報デジタル版掲載  2023.11

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    SDGs:

  • プライム-ブースト型粘膜ワクチンの開発 Internet

    Qlife Pro医療ニュース  2023.11

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  • プライム-ブースト型粘膜ワクチンの開発 Internet

    Rakuten infoseek News  2023.11

  • プライム-ブースト型粘膜ワクチンの開発

    Mapionニュース  2023.11

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  • プライム-ブースト型粘膜ワクチンの開発 Internet

    マイナビ Tech+  2023.11

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