Analysis on a new immunoregulatory mechanism to control pathogenic T cell repertoires

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H01051
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Keio University
• Principal Investigator: TAKAHASHI Hayato 慶應義塾大学, 医学部(信濃町), 准教授 (40398615)
• Co-Investigator(Kenkyū-buntansha): 谷口 智憲 京都大学, 医学研究科, 特定講師 (40424163) ; 舩越 建 慶應義塾大学, 医学部(信濃町), 准教授 (80365353) ; 山上 淳 慶應義塾大学, 医学部(信濃町), 講師 (80327618)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 免疫寛容 / 免疫制御 / T細胞 / 天疱瘡 / 自己免疫疾患

Outline of Final Research Achievements

The aim of this study is to elucidate the various immune tolerance mechanisms that we have identified and to use them to treat autoimmune diseases and to enhance cancer immunotherapy. In particular, we have shown that the immune tolerance mechanism functioning in peripheral tissues operates in an antigen-specific manner to eliminate autoreactive T cells, and that the molecule OX40, which is expressed by regulatory T cells, is important as a part of this mechanism. Furthermore, this mechanism was able to eliminate pathological T cells more efficiently when functioning repeatedly, suggesting the existence of a memory of immune tolerance mechanisms. Furthermore, we identified cholesterol metabolism-related molecules that act as brakes on cancer immunity. These results were expected to be useful for the development of the treatment in intractable diseases and cancer.

Free Research Field

皮膚免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒト自己免疫疾患で標的とされている自己抗原に対する抗原特異的な末梢性免疫寛容機構の一端をマウスモデルで明らかにできた点が、人工的に作成された従来の自己免疫モデルでの成果と大きく異なる。特に、今回明らかにできた制御性T細胞が発現するOX40分子が重要な分子であった点は、今後の免疫疾患治療戦略上、有益な成果であったと考えられた。また、本研究を通じて、免疫制御機構とコレステロール代謝の接点を明らかにできた。従来知られてこなかった、コレステロール代謝を利用した免疫制御機構を明らかにでき、今後の疾患制御法開発の戦略に新たな研究領域を確立できたことは、学術的にも大きな意義があった。