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.
Bibliographical noteFunding Information:
This study was supported by the Basic Science Research Program ( 2015R1A2A1A10056084 to S.-.J.H. and 2016R1A2B4014230 to T.-.D.K.) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning . This study was also supported by the Korean Health Technology R&D Project ( HI14C2680 and HI15C0493 to S.-.J.H.) through the Korean Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare and by a National Research Council of Science & Technology (NST) grant ( CRC-15-02-KRIBB to T.-.D.K.).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)