| Project/Area Number |
16K09897
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 関節リウマチ / 自然リンパ球 / Th17サイトカイン / CCR6 / ILC3 / IL-17 / IL-22 / arthritis / IL-17A |
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| Outline of Final Research Achievements |
Recent studies show that Innate Lymphoid Cells (ILCs) contribute to development of chronic inflammation and autoimmune disease. In this study, we assessed ILC function in the pathogenesis of rheumatoid arthritis (RA). In the mouse of collagen-induced arthritis (CIA) , the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p=0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p=0.015). In RA patients, relatively high levels of CCR6+ ILC3s in SF were positively correlated with tender joint count (TJC) and swollen joint count (SJC) (ρ=0.689, p=0.0032 and ρ=0.644, p=0.0071 respectively). These data suggest that CCR6+ ILC3s are positively associated with RA development through production of IL-17 and IL-22.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、関節リウマチの治療成績は飛躍的に改善したが、未だ臨床的寛解に到達できず、関節破壊が進行する症例が少なからず存在する。この理由の一つに、未だ解明できていない病態があり、その制御が不十分な可能性がある。今回我々は、新規細胞系列であるILCに着目した。この細胞系列は、ヘルパーT細胞に非常に類似した機能を有している。本研究にて、関節炎発症においてCCR6+ILC3が関与している可能性が新たに示唆された。これにより、関節リウマチの病態の理解が進むだけでなく、関節リウマチの新たな治療戦略構築にも役立つと考えられる。
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