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Elucidation of intestinal immunoregulatory mechanism in arthritis

Research Project

Project/Area Number 18K16644
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionYamagata University

Principal Investigator

Naganuma Yasushi  山形大学, 医学部, 客員研究員 (10463811)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腸管免疫 / 関節リウマチ / 腸内細菌叢 / 関節炎
Outline of Final Research Achievements

In this study, we analyzed the intestinal immune system and intestinal flora using a mouse collagen-induced arthritis (CIA) model with the goal of preventing the onset and relapse of rheumatoid arthritis (RA). After preparing the CIA model, immune cells were collected before and after the onset of CIA, after remission, and after relapse, and the kinetics and function were analyzed. Furthermore, joint tissues and blood were collected, and immunohistological evaluation and cytokine quantification were performed. In addition, feces were collected at any time, and intestinal microflora was analyzed using a next-generation sequencer. Immune cells, cytokines, and intestinal flora also fluctuated significantly with the onset, remission, and relapse of arthritis. In particular, it was suggested that the dynamics of the intestinal immune system differ between the initial onset and relapse.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは未だ根治的治療法はない。本研究により関節リウマチモデルにおける腸管免疫系の時系列変化が明らかになった。本研究の社会的意義として、将来的に関節リウマチ患者の便を回収、解析することにより特徴的な細菌の存在を明らかとし、関節リウマチの病勢を予測することが可能になると考えられる。また、特に病勢が強い時期に特徴的な腸内細菌を抑制し、腸管免疫を修飾することにより関節リウマチの治療につながる可能性が示唆された。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] intestinal immunity and flora in a collagen-induced mouse parthritis model: differences during arthritis progression.2019

    • Author(s)
      Nemoto N, Takeda Y, Nara H, Araki A, Gazi Y, Takakubo Y, Naganuma Y, Takagi M, Asao H
    • Journal Title

      Int Immunol.

      Volume: 32 Issue: 1 Pages: 49-56

    • DOI

      10.1093/intimm/dxz058

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Changes of intestinal immunity during arthritic progression in mouse model.2018

    • Author(s)
      Nobuhito NEMOTO, Yuji TAKEDA, Hidetoshi NARA, Akemi ARAKI, Md. Yeashin GAZI, Yuuya TAKAKUBO, Michiaki TAKAGI, Hironobu ASAO
    • Organizer
      ORS annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Can the intestine save the joints ? : From the viewpoints of intestinal immunity during arthritic progression in mouse model.2018

    • Author(s)
      Nobuhito NEMOTO, Yuji TAKEDA, Hidetoshi NARA, Akemi ARAKI, Md. Yeashin GAZI, Yuuya TAKAKUBO, Michiaki TAKAGI, Hironobu ASAO
    • Organizer
      第91回日本整形外科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウス関節炎モデルにおける腸管免疫系の時系列解析2018

    • Author(s)
      根本 信仁、武田 裕司、奈良 英利、荒木 明美、Gazi Yeashin、高窪 祐弥、高木 理彰、浅尾 裕信
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Toll-like receptors and immune-cells in rheumatoid synovial tissues treated by tocilizumab (TCZ)2018

    • Author(s)
      Yuya Takakubo; Tomoto Suzuki; Hiroharu Oki; Nobuhito Nemoto; Yasushi Naganuma; Yuta Suzuki; Kan Sasaki; Michiaki Takagi
    • Organizer
      第4回日本骨免疫学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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