| Project/Area Number |
18K16145
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Nakashima Ran 京都大学, 医学研究科, 助教 (10599525)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 皮膚筋炎 / 抗MDA5抗体 / フラクタルカイン / CX3CR1 / 単球 / 筋炎特異的自己抗体 |
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| Outline of Final Research Achievements |
Anti-MDA5-positive dermatomyositis (DM) patients showed significantly higher serum CX3CL1 (fractalkine) levels than anti-MDA5-negative DM. Even compared among patient groups defined with each myositis-specific autoantibodies, anti-MDA5-positive group tended to show the highest level of CX3CL1. Moreover, among anti-MDA5-positive patients, CX3CL1 increased much more in the intractable cases than in the favorable group during the disease course. Peripheral non-classical monocyte (CD14 low, CD16 high) was significantly increased in anti-MDA5-poitive patients, but their expression of CX3CR1 seemed to be reduced, which might suggest that monocytes had been migrated into the tissue lesion. We are proceeding immune histopathological examination on the CX3CR1-positive monocytes or macrophages, assessing their distribution and association with CX3CL1 positive cells.
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| Academic Significance and Societal Importance of the Research Achievements |
抗MDA5抗体陽性皮膚筋炎は、膠原病の中でも最も予後不良な一群であり、急速進行性間質性肺炎を合併し短期間で死亡するリスクが高い。同疾患に対する治療は従来の免疫抑制薬を組み合わせて行われるが、未だに救命できない症例が存在し、新規治療法の開発が切に望まれている。病態背景には単球やマクロファージの異常活性化が示唆されるが、その機序は明らかではない。一方、ケモカインと細胞接着分子の2つの活性を持つCX3CL1とそのレセプターCX3CR1は単球の遊走や分化において重要な役割を果たすことが示唆されている。本病態にCX3CL1-CX3CR1が関与することを示すことができれば、新規治療戦略につながると考えた。
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