| Project/Area Number |
18K08263
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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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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Okiyama Naoko 筑波大学, 医学医療系, 講師 (10581308)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 | 自己免疫疾患 / 炎症性筋疾患 / 疾患モデル / 自己免疫 / 皮膚筋炎 / 間質性肺炎 / マウスモデル / 自己免疫性筋炎 / 細胞傷害性T細胞 / パーフォリン / 養子移入 / T細胞 / B細胞 / 自己抗原 |
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| Outline of Final Research Achievements |
To investigate whether autoimmunity to TIF1γ, a ubiquitous nuclear autoantigen for myositis-specific autoantibodies detected in patients with dermatomyositis (DM) is pathogenetic for inflammatory myopathy. Immunization with TIF1γ-induced experimental myositis successfully in wild-type mice. The incidence and severity of myositis were significantly lower in β2-microglobulin-null or CD8-depleted mice, while Igμ-null mice developed myositis normally. Adoptive transfer of CD8+ T cells induced myositis in recipients, while transfer of CD4+ T cells or IgG did not. Treatment with tofacitinib inhibited TIF1γ-induced myositis.
Here we show that TIF1γ is immunogenic enough to cause experimental myositis, in which CD8+ T cells and type I interferons, but not CD4+ T cells, B cells or antibodies, are required. This murine model would be a tool for understanding the pathologies of DM.
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| Academic Significance and Societal Importance of the Research Achievements |
抗TIF1γ抗体陽性の皮膚筋炎患者は、小児であれば筋力低下が顕著であること、成人であれば内臓悪性腫瘍を合併していることが知られていますが、現状の治療としては、非特異的免疫抑制療法しか存在しません。本研究で確立したモデルマウスは、患者の体内で起こっている自己免疫機構を忠実に模しており、より効果的で、かつ悪性腫瘍治療の邪魔をしない、筋炎治療法の開発に貢献することが期待されます。
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