Elucidating the mechanisms of effector differentiation and tissue accumulation of regulatory T cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16601
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Murakami Ryuichi 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (60800505)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 制御性T細胞 / Foxp3 / BATF / T細胞受容体

Outline of Final Research Achievements

In this study, we aimed to elucidate the molecular mechanism of BATF/Foxp3-mediated effector Treg cell differentiation, proliferation and tissue accumulation. We demonstrated that T cell receptor (TCR) signal was essential for BATF/Foxp3-mediated effector Treg cell differentiation, proliferation and tissue accumulation both in vitro and in vivo. Besides, we identified BATF/Foxp3 co-target genes which were highly expressed on effector Treg cells and were associated with lysosome pathway. Thus, it was suggested that BATF cooperates with Foxp3 under TCR signal and promote effector Treg cell differentiation, proliferation and tissue accumulation presumably through activation of lysosome pathway.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

Foxp3が免疫抑制能を有する制御性T細胞に選択的に発現する分子であることから、我々が本研究で明らかにしたBATFとFoxp3の協調による活性化型制御性T細胞分化・増殖・組織集積促進の分子基盤を制御することで、制御性T細胞のみを選択的に活性化もしくは抑制し様々な疾患治療に役立てることができると思われる。