| Project/Area Number |
18K08385
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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 54020:Connective tissue disease and allergy-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 全身性血管炎 / 制御性T細胞 / 活性酸素 / Sirt1 / アンチエイジング / 抗酸化作用 / mTOR / レスベラトロール |
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| Outline of Final Research Achievements |
We explored the etiological mechanism for impairing functional ability of regulatory T cells (Tregs), in order to improve Tregs function, in ANCA-associated vasculitis (AAV). The phosphorylation of mTOR was found to be induced ascribable to increase in reactive oxygen species (ROS) expression and decrease in the activity of Sirt1 in Tregs, leading to impairing their suppressive function in AAV. In Tregs treated with resveratrol (RVL), their functional recovery was demonstrated; and moreover, suppressed phosphorylation of mTOR, as well as reduced ROS expression and increased activation of Sirt1, was simultaneously shown in Tregs. This study suggests that antioxidative and anti-immune aging effects by RVL may contribute to improve suppressive ability of Tregs in AAV.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、AAVをはじめリウマチ膠原病領域における治療戦略は進歩を続けているが、未だ完治は難しく再発再燃が多くの患者で経験される。本研究の成果は、本来私たちに備わった免疫制御機構の中心を担う制御性T細胞（Treg）に焦点を当てた研究であり、より生理的な手法でTregの機能回復を試みた結果であることから、将来の免疫調整療法の開発に寄与する可能性が期待される。またこの手法が治療薬の開発に結びつけば、併用によって副腎皮質ステロイドを含む従来の免疫抑制薬の減量効果に寄与できる可能性も考慮される。
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