miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation

Cell Reports

Young Ho Ban¹  Sang-Jun Ha¹  Jun Chang²  Philip D. Greenberg³  Seok-Min Kim⁴  In-Pyo Choi⁴  Se-Chan Oh⁴  Tae-Don Kim⁴  Sang-Hwan Seo⁴ 

[1] Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul 03722, Korea;Division of Life & Pharmaceutical Sciences, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 03760, Korea;Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98195, USA;Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea;

关键词: miR-150;    Foxo1;    CD8;    memory;    differentiation;    acute;    infection;    primary immune response;    recall;    LCMV;   

DOI  :  10.1016/j.celrep.2017.08.065

来源: DOAJ

【 摘 要 】

MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8+ T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8+ T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8+ T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8+ T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8+ T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics.

【 授权许可】

Unknown