Construction of effective induction of immune tolerance to rheumatoid arthritis using fingolimod
| Project/Area Number |
19K08897
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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 | Setsunan University |
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Principal Investigator |
Yoshida Yuya 摂南大学, 薬学部, 講師 (50581435)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | フィンゴリモド / 免疫寛容 / 寛解 / interleukin-10 / 骨髄由来免疫抑制細胞 / IL-10 / FTY720 |
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| Outline of Research at the Start |
FTY720と病因抗原の併用療法による免疫寛容誘導機構の解明を目的に、本併用治療で増加する抑制系細胞のIL-10高産生性T細胞および骨髄由来免疫抑制細胞（myeloid-derived suppressor cells; MDSC）を特徴付ける分子を同定し、それら細胞の機能解析および病因T細胞との相互作用を明らかとする。また、FTY720と病因抗原の併用治療による免疫寛容誘導の一般性について、他の自己免疫疾患のモデル動物を用いて明らかとする。
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| Outline of Final Research Achievements |
We identified and characterized immunosuppressive cells that were increased by combination treatment with fingolimod (FTY720) and pathogenic antigen. Among GITR+CD25-CD4+T cells, the number of CD44+CD62L-CD122+CD130-CD279+ cells with extremely high IL-10 expression was increased. The cells also had high IFN-γ and IL-4 expression and effector activity, but as a GITR+CD25-CD4+ T cell population, they were inhibitory to T cell proliferation due to soluble factors. The percentage of CD11c-CD369+CD11b+Gr-1+ cells with high T cell proliferative suppressive capacity was also increased. The induction of these cells with high suppressive capacity was suggested to construct immune tolerance.
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| Academic Significance and Societal Importance of the Research Achievements |
関節リウマチに対して、長期的に寛解状態が維持できる治療戦略の開発が求められている。即ち、再燃の原因となる病因リンパ球が活性化しないような体内環境を根付かせることが理想的である。これまでの研究で、FTY720と病因抗原の併用治療が、その事象を実現し得ることを見いだしつつあった。本申請課題では、本併用治療がその効果を発揮する上で重要な細胞集団のより詳細な特性に関する知見を集積できた。本研究成果は、効果的な免疫寛容の誘導戦略の構築につながる重要な知見であると考えられる。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Therapeutic Strategy for Rheumatoid Arthritis by Induction of Myeloid-Derived Suppressor Cells with High Suppressive Potential2022
Author(s)
Shohei Nakano, Norihisa Mikami, Mai Miyawaki, Saho Yamasaki, Shoko Miyamoto, Mayu Yamada, Tomoya Temma, Yousuke Nishi, Arata Nagaike, Seijun Sakae, Takuya Furusawa, Ryoji Kawakami, Takumi Tsuji, Takeyuki Kohno, Yuya Yoshida
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 45
Issue: 8
Pages: 1053-1060
DOI
ISSN
0918-6158, 1347-5215
Year and Date
2022-08-01
Related Report
Peer Reviewed / Open Access
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