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Establishment of an immune regulation of T cell function through gut microbiota modulation

Research Project

Project/Area Number 25461488
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Shimizu Jun  聖マリアンナ医科大学, 医学部, 准教授 (30509964)

Co-Investigator(Renkei-kenkyūsha) Takai Kenji  聖マリアンナ医科大学, 医学部, (客員)教授 (60121167)
Fujiwara Naruyoshi  聖マリアンナ医科大学, 医学部, 助教 (50365425)
Arimitsu Nagisa  聖マリアンナ医科大学, 医学部, 助教 (40408688)
Takada Erika  聖マリアンナ医科大学, 医学部, 研究技術員 (90398959)
Hirotsu Chieko  聖マリアンナ医科大学, 医学部, 研究技術員 (90647174)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腸内細菌叢メタゲノミクス / T細胞 / ベーチェット病 / Tリンパ球 / 腸内細菌メタゲノミクス / Th17細胞 / 炎症性腸疾患 / 再発性多発軟骨炎 / 全身性エリテマトーデス
Outline of Final Research Achievements

We have reported that T cell differentiation was skewed in the peripheral blood of patients with Behcet’s disease (BD). We hypothesized that gut microbiota of BD patients involved in the skewed T cell differentiation from a review of the literature. We conducted metagenomic analysis of microbiota using next generation sequencer. We showed that the phylum Actinobacteria and the genus Bifidobacterium were prevalent in BD patients with statistical significance. The order Clostridia and the genus Megamonas were prevalent in normal individuals with statistical significance. Bacterial diversity of each sample was comparable in BD patients and normal individuals and the two group’s plots of PcoA had a significant distance as beta diversity. These data suggest that the compositional changes of gut microbes may be one type of dysbiosis (unfavorable microbiota alteration) in patients with BD. The dysbiosis may have an association with the pathophysiology of BD.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013

All Journal Article (13 results) (of which Acknowledgement Compliant: 6 results,  Peer Reviewed: 12 results,  Open Access: 5 results) Presentation (2 results)

  • [Journal Article] ヒトアレルギー・免疫疾患におけるTh17 細胞異常と腸内細菌叢Dysbiosis2016

    • Author(s)
      清水潤、久保田孝雄、鈴木登
    • Journal Title

      アレルギーの臨床

      Volume: 36 Pages: 147-152

    • Related Report
      2015 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Bifidobacteria Abundance-Featured Gut Microbiota Compositional Change in Patients with Behcet’s Disease2016

    • Author(s)
      1.Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0153746-e0153746

    • DOI

      10.1371/journal.pone.0153746

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet's disease.2015

    • Author(s)
      7.Shimizu J, Takai K, Takada E, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
    • Journal Title

      Clin Rheumatol.

      Volume: 34 Issue: 7 Pages: 1-7

    • DOI

      10.1007/s10067-015-2966-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] large-scale survey of patients with relapsing polychondritis in Japan.2014

    • Author(s)
      Hiroshi Oka, Yoshihisa Yamano, Jun Shimizu, Kazuo Yudoh, Noboru Suzuki.
    • Journal Title

      Inflammation and Regeneration

      Volume: 34 Pages: 149-156

    • NAID

      130004943860

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neurological Involvement of Relapsing polychondritis in Japan: An Epidemiological Study.2014

    • Author(s)
      Noboru Suzuki, Jun Shimizu, Hiroshi Oka, Yoshihisa Yamano, Kazuo Yudoh.
    • Journal Title

      Inflammation and Regeneration

      Volume: 34 Pages: 206-208

    • NAID

      130004943867

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pax7 Gene Induction Rapidly Regulates Myocyte Homeostasis in Human Induced Pluripotent Stem (iPS) Cells.2014

    • Author(s)
      Misawa H, Saito A, Shimizu J, Iinuma M, Shiratsuchi T, Fujiwara N, Takai K, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Beppu M, Suzuki N.
    • Journal Title

      St. Marianna Medical Journal.

      Volume: 5 Pages: 59-67

    • NAID

      40020336414

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] T cell protein tyrosine phosphatase (TCPTP) regulates phosphorylation of Txk, a tyrosine kinase of the Tec family.2014

    • Author(s)
      Maruyama T, Shimizu J, Suzuki N.
    • Journal Title

      Inflammation and Regeneration

      Volume: 34 Pages: 240-246

    • NAID

      130004943871

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis.2014

    • Author(s)
      Sato T, Yamano Y, Tomaru U, Shimizu Y, Ando H, Okazaki T, Nagafuchi H, Shimizu J, Ozaki S, Miyazawa T, Yudoh K, Oka H, Suzuki N.
    • Journal Title

      Mod Rheumatol

      Volume: 24(1) Issue: 1 Pages: 129-136

    • DOI

      10.3109/14397595.2013.852854

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease.2013

    • Author(s)
      Shimizu J, Kaneko F, Suzuki N.
    • Journal Title

      Genet Res Int

      Volume: 2013 Pages: 363859-363859

    • DOI

      10.1155/2013/363859

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells.2013

    • Author(s)
      Fujiwara N, Shimizu J, Takai K, Arimitsu N, Saito A, Kono T, Umehara T, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
    • Journal Title

      Neurosci Lett.

      Volume: 13 Pages: 947-6

    • DOI

      10.1016/j.neulet.2013.10.043

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of Motor Neurons Derived from Human iPS Cells into Total Transection Model of Spinal Cord Injury in Mice.2013

    • Author(s)
      Umehara T, Arimitsu N, Iinuma M, Shimizu J, Takai K, Fujiwara N, Saito A, Kono T, Ueda Y, Wakisaka S, Suzuki T, Beppu M, Suzuki N.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 21-30

    • NAID

      40019942497

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human iPS Cell Derived Neurons with Cortical Motor Neuron Phenotype are Relevant for Functional Recovery of Hemiplegic Mice with Injured Motor Cortex.2013

    • Author(s)
      T, Arimitsu N, Shimizu J, Takai K, Fujiwara N, Umehara T, Saito A, Ueda Y, Wakisaka S, Suzuki T, Hashimoto T, Tanaka Y, Suzuki N.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 31-40

    • NAID

      40019942503

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IGFII/Akt Signaling Regulates Myocyte Homeostasis in Human Induced Pluripotent Stem (iPS) Cells.2013

    • Author(s)
      Saito A, Shimizu J, Fujiwara N, Takai K, Arimitsu N, Umehara T, Kono T, Misawa H, Ueda Y, Wakisaka S, Suzuki T, Beppu M, Suzuki N.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 41-48

    • NAID

      40019942512

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ベーチェット病におけるBifidobacterium属優位の特徴的な腸内細菌叢2016

    • Author(s)
      清水潤、久保田孝雄、鈴木登
    • Organizer
      第60回日本リウマチ学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] ベーチェット病リンパ球におけるTh17細胞関連サイトカインとIL-23受容体の動態2013

    • Author(s)
      清水 潤、鈴木 登
    • Organizer
      日本リウマチ学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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