2023 Fiscal Year Final Research Report
Regulation of experimental autoimmune uveoretinitis (EAU) by antigen specific regulatory T cells
Project/Area Number |
21K16905
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56060:Ophthalmology-related
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Research Institution | Kyorin University |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | ぶどう膜炎 |
Outline of Final Research Achievements |
Regulatory T cells (Tregs) have important roles for maintaining immunological tolerance. Systemic administration of cyclin-dependent kinase (CDK) 8/19 inhibitor AS2863619 (hereafter referred to as AS) is capable of increasing Foxp3+CD4+ Tregs in vitro and in vivo, exerting immune regulations. In this study, we investigated the anti-inflammatory effect of AS administration on experimental autoimmune uveoretinitis (EAU). Although the rate of Tregs in vivo was not increased in EAU-induced mice treated with AS, oral administration of AS was effective for amelioration of EAU. In addition, AS significantly reduced IFN-gamma and IL-17 production in vitro in draining lymph-node cells. The present study demonstrate that CDK8/19 may be new therapeutic targets for autoimmune uveoretinitis.
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Free Research Field |
眼科学
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Academic Significance and Societal Importance of the Research Achievements |
現在、非感染性ぶどう膜炎による治療はステロイド薬の点眼や全身投与、免疫抑制薬(シクロスポリン)、生物学的製剤(アダリムマブ)が用いられているが、これらの治療を行っても効果が不十分、また全身副作用のため減量・中止を要する症例が存在する。今回用いたAS2863619はCDK8/19に対する阻害作用をもち、ぶどう膜炎の動物モデルである実験的自己免疫性ぶどう膜網膜炎に対する炎症抑制効果を示した。先行研究では多発性硬化症など他の免疫疾患モデルでもAS2863619が抗炎症作用を示すことが報告されており、今後CDK8/19がヒト自己免疫疾患の新たな標的分子となる可能性が示唆された。
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