Study of the function and development of regulatory T cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 16H06295
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: Shimon Sakaguchi 大阪大学, 免疫学フロンティア研究センター, 特任教授(常勤) (30280770)
• Co-Investigator(Kenkyū-buntansha): ウィング ジェイムス 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (00648694) ; 市山 健司 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (60777960) ; 三上 統久 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (20710388)
• Project Period (FY): 2016-04-26 – 2021-03-31
• Keywords: 自己免疫寛容 / 制御性T細胞 / 自己免疫疾患 / Foxp3 / エピジェネティクス

Outline of Final Research Achievements

This project has attempted to elucidate the molecular basis of immunosuppressive function and development of regulatory T cells (Tregs). In particular, we clarified that regulation of genomic structures at the Foxp3 locus based on Treg-specific epigenome is essential for early development of Tregs in the thymus. We also showed that functionally stable Tregs can be efficiently induced from antigen-specific conventional T cells by removal of certain signaling pathways. This enables a novel immunotherapy with functionally stable induced Tregs.
We also proved that selective depletion of tumor-infiltrating effector Tregs, which hamper effective anti-tumor immunity, can evoke and enhance anti-tumor immune responses. In addition, we found that autoimmune disease-associated SNPs are frequently accumulated in the Treg-specific DNA demethylation regions in human Tregs, suggesting the importance of genetic variations in Treg function for determining genetic susceptibility to autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、Tregの分化および免疫抑制機構の基礎的理解を進めた。その結果、Tregを標的とし、その量的・機能的減弱による、癌、病原微生物に対する新しい免疫賦活法の開発、一方、Tregの抗原特異的増殖、あるいは抗原特異的T細胞からの機能安定型Tregの分化誘導による自己免疫疾患や移植臓器拒絶反応に対する革新的治療法の開発、医療応用が期待できる。