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Histological changes of the synovial tissues and involvement of acquired immunity in a murine model for rheumatoid arthritis induced by infection with Mycoplasma fermentans.

Research Project

Project/Area Number 17K16217
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionKawasaki Medical School

Principal Investigator

Yahagi Ayano  川崎医科大学, 医学部, 助教 (10584873)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords関節リウマチ / gp130F759 / Mycoplasma fermentans感染 / 自然免疫 / 獲得免疫 / 関節滑膜組織 / 関節炎動物モデル / Mycoplasma fermentans / 線維芽細胞様滑膜細胞 (FLS) / Col1a1-ECFP / ノックインモデル / マイコプラズマ
Outline of Final Research Achievements

Using knock-in mice gp130F759 having the mutant gp130Y759F, we established an arthritis model, in which development of arthritis is accelerated by systemic infection with Mycoplasma fermentans (Mf) at 3 M.O., much earlier than spontaneous arthritis. To detect fibroblast-like synoviocytes(FLS), we crossed Col1a1-ECFP mice with gp130F759 to make Col1a1-ECFP/gp130F759. Increases of FLS after infection were detected in superficial lining and sublining of the synovium but phospho-stat3 was not detected. We examined which immune system, innate or acquired, plays critical roles in the earliest phase of arthritis induced by Mf infection. To deplete T, B cells or neutrophils, monoclonal antibodies were injected intraperitoneally 9 days after infection. Only depletion of neutrophils prevented both development of arthritis and increases of synovial T and B cells in the knee, suggesting critical and pre-requisite roles of neutrophils in transition from innate to immune systems before onset of RA.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチの関節破壊発生前に自然免疫が関与する時期と獲得免疫の免疫寛容が破綻する時期の2病相の存在が認識されている。遺伝子改変マウス関節炎モデルに低病原性微生物を感染させる実験系で、好中球が関節炎発症促進及び獲得免疫系細胞の増加に必須であることを証明した。関節リウマチを始めとする全身性自己免疫疾患の発症機構において同様の微生物-自然免疫-獲得免疫の連関の存在が示唆され、新たな治療標的を提供する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] IL-6-PAD4 axis in the earliest phase of arthritis in knock-in gp130F759 mice, a model for rheumatoid arthritis2019

    • Author(s)
      Yahagi Ayano、Saika Taro、Hirano Hiroyasu、Takai-Imamura Miwa、Tsuji Fumio、Aono Hiroyuki、Iseki Masanori、Morita Yoshitaka、Igarashi Hideya、Saeki Yukihiko、Ishihara Katsuhiko
    • Journal Title

      RMD Open

      Volume: 5 Issue: 2 Pages: e000853-e000853

    • DOI

      10.1136/rmdopen-2018-000853

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production2019

    • Author(s)
      Yang Qianting、Liao Mingfeng、Wang Wenfei、Zhang Mingxia、Chen Qi、Guo Jiubiao、Peng Bin、Huang Jian、Liu Haiying、Yahagi Ayano、Xu Xingzhi、Ishihara Katsuhiko、Cooper Andrea、Chen Xinchun、Cai Yi
    • Journal Title

      mBio

      Volume: 10 Issue: 4

    • DOI

      10.1128/mbio.01949-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] IL-6-PAD4 axis: IL-6 dependent PAD4 production in neutrophils at the earliest phase of arthritis in gp130F7592019

    • Author(s)
      Ayano Yahagi, Taro Saika, Masanori Iseki, Katsuhiko Ishihara
    • Organizer
      The 48th Annual Meeting of the Japanese for Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CX3CR1-eGFP+ macrophage-like synoviocytes in gp130F759, a mouse model for rheumatoid arthritis2019

    • Author(s)
      Ayano Yahagi, Yujiro Yokoyama, Noritaka Tsunematsu, Masanori Iseki, Katsuhiko Ishihara
    • Organizer
      The 26th International Symposium on Molecular Cell Biology of Macrophages
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 関節リウマチ(RA)モデルgp130F759の最初期変化とM.fermentansの影響2019

    • Author(s)
      矢作 綾野、井関 將典、石原 克彦
    • Organizer
      第34回自己免疫研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Accelerated onset of arthritis by systemic infection of Mycoplasma fermentans in the knock-in mice gp130F7592018

    • Author(s)
      Ayano YAHAGI, Taro SAIKA, Hiroyasu HIRANO, Masanori ISEKI, Katsuhiko ISHIHARA
    • Organizer
      IMMUNOLOGY 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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