| Project/Area Number |
17K16217
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
Yahagi Ayano 川崎医科大学, 医学部, 助教 (10584873)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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