Construction of effective induction of immune tolerance to rheumatoid arthritis using fingolimod

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Setsunan University
• Principal Investigator: Yoshida Yuya 摂南大学, 薬学部, 講師 (50581435)
• Project Period (FY): 2019-04-01 – 2022-03-31
• 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

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.

Free Research Field

免疫学、病態生化学

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。