Mechanisms of long-term survival of self-reactive helper T cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Keio University
• Principal Investigator: CHIKUMA Shunsuke 慶應義塾大学, 医学部(信濃町), 准教授 (50437208)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 自己免疫疾患 / ヘルパーＴ細胞

Outline of Final Research Achievements

IL-17 producing helper T cells (Th17) are suggested in persistent autoimmune diseases. We found that autoreactive Th17 are preferentially maintained and activated in lymphopenic mice and caused severe autoimmune diseases. In addition, mice treated with a cocktail of antibiotics that depleted intestinal microbiota showed almost complete protection from Th17-mediated autoimmunity. Our current data suggest that autoreactive T cells are maintained by intestinal microbiota. Modulating particular intestinal bacteria may provide novel therapy for many autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

乾癬、リウマチ性関節炎、全身性エリテマトーデス、多発性硬化症といった慢性の自己免疫疾患は近年増加の一途をたどり、この病態解明は社会的に緊急かつ重要な課題である。マウスを用いて自己反応性Th17が長期生存し、慢性皮膚炎を起こすモデルを確立できた。今後は、このモデルを用いて自己免疫疾患の新規治療法を研究する予定である。また、Th17の生存や活性化に関わる菌およびその抗原などを同定できれば、自己免疫疾患のさらなる理解や治療法につながると考えられる。