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

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): Young Ho Ban, Se-Chan Oh, Sang-Hwan Seo, Seok-Min Kim, In-Pyo Choi, Philip D. Greenberg, Jun Chang, Tae-Don Kim, Sang-Jun Ha
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.

Graphical abstract

Teaser

MicroRNAs regulate CD8⁺ T cell responses, but their targets and function in CD8⁺ T cell differentiation are unclear. Ban et al. identify miR-150 as a regulator of CD8⁺ T cell differentiation and show that it represses the expression of Foxo1, an inducer of TCF1 that promotes the memory CD8⁺ T cells formation.


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