2022 Fiscal Year Final Research Report
The role of Arf pathway in the maintenance of T cell survival
Project/Area Number |
21K15474
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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 49070:Immunology-related
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Research Institution | Kansai Medical University |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Keywords | T細胞 / 細胞死 / Arf / 自己免疫疾患 / 感染応答 |
Outline of Final Research Achievements |
We investigated the mechanism underlying enhanced cell death in Arf1/Arf6 double-deficient CD4+ T cells (Arf-KO cells) during TCR activation. Naive Arf-KO T cells showed metabolic pattern similar to control cells, whereas activated Arf-KO T cells exhibited enhanced oxidative phosphorylation. Rapamycin protected cell death in Arf-KO cells, strongly suggesting that metabolic imbalance is the main cause of enhanced cell death in Arf-KO cells. Consistent with the finding that survival of Arf-KO cells was maintained in the presence of IL-21, the survival of Tfh in lymph nodes was maintained even under Th1-type or Th2-type immune conditions. Actually, we found that Arf-KO mice are resistant to both Th1-type and Th2- type infections.
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Free Research Field |
免疫学
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Academic Significance and Societal Importance of the Research Achievements |
Arf1・Arf6が全ての状態のT細胞ではなく、活性化T細胞特異的に生存維持に働くこと、その背景に代謝リプログラミングの異常があることを明らかにした点に高い学術的意義がある。既に、T細胞特異的なArf1・Arf6の二重欠損は、自己免疫疾患をほぼ完全に抑制することを報告している。一方で、Th1やTh2を介した感染応答は、Arf1・Arf6を欠損してもある程度維持されていることを本研究で見出した。以上の知見は、Arf1・Arf6が制御する活性化T細胞の生存維持機構を標的とすることで、生体防御の維持と自己免疫疾患の抑制を両立する新たな治療法開発に繋がる可能性を強く示唆し、社会的意義がある。
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