CX3CL1-CX3CR1 plays an important role in the pathophysiology of anti-MDA5-positive dermatomyositis
| 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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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment2020
Author(s)
Shirakashi M, Nakashima R (Corresponding author), Tsuji H, Tanizawa K, Handa T, Hosono Y, Akizuki S, Murakami K, Hashimoto M, Yoshifuji H, Ohmura K, Mimori T.
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Journal Title
Rheumatology (Oxford) .
Volume: 59
Issue: 11
Pages: 3284-3292
DOI
Related Report
Peer Reviewed
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[Journal Article] Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis.2020
Author(s)
Tsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H, Hirata S, Nojima T, Sugiyama E, Hatta K, Taguchi Y, Katayama M, Tanizawa K, Handa T, Uozumi R, Akizuki S, Murakami K, Hashimoto M, Tanaka M, Ohmura K, Mimori T.
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Journal Title
Arthritis Rheumatol.
Volume: 72
Issue: 3
Pages: 488-498
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum neopterin as well as ferritin, soluble interleukin-2 receptor, KL-6 and anti-MDA5 antibody titer provide markers of the response to therapy in patients with interstitial lung disease complicating anti-MDA5 antibody-positive dermatomyositis.2018
Author(s)
Nishioka A, Tsunoda S, Abe T, Yoshikawa T, Takata M, Kitano M, Matsui K, Nakashima R, Hosono Y, Ohmura K, Mimori T, Sano H.
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Journal Title
Mod Rheumatol.
Volume: -
Issue: 5
Pages: 814-820
DOI
Related Report
Peer Reviewed
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[Presentation] 抗MDA5抗体陽性間質性肺炎合併皮膚筋炎患者に対するステロイド、タクロリムス、シクロフォスファミド併用療法の有効性と安全性に関する多施設前向き研究2019
Author(s)
辻 英輝, 中嶋 蘭, 細野 祐司, 井村 嘉孝, 八木田 正人, 吉藤 元, 平田 信太郎, 野島 崇樹, 杉山 英二, 八田 和大, 田口 義夫, 片山 昌紀, 秋月 修治, 村上 孝作, 橋本 求, 田中真生, 大村 浩一郎, 三森 経世
Organizer
第63回日本リウマチ学会総会・学術集会
Related Report
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[Presentation] Efficacy and Safety of Combined Immunosuppressive Therapy with High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Disease Accompanied by Anti-MDA5-Positive Dermatomyositis -A Multicenter Prospective Study -2018
Author(s)
Hideaki Tsuji, Ran Nakashima, Yoshitaka Imura, Masato Yagita, Hajime Yoshifuji, Shintaro Hirata, Takaki Nojima, Eiji Sugiyama, Kazuhiro Hatta, Yoshio Taguchi, Masaki Katayama, Shuji Akizuki, Kosaku Murakami, Motomu Hashimoto, Masao Tanaka, Koichiro Ohmura, Tsuneyo Mimori
Organizer
American College of Rheumatology 2018 Annual Meeting
Related Report
Int'l Joint Research
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