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

Abstract

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.

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