MiR-150 negatively regulates CD8+ T cell memory formation

MicroRNAs play an important role in CD8+ T cell differentiation and anti-viral immune responses. However, how microRNAs regulate CD8+ T cell memory formation remains poorly defined. Here, by microRNA profiling of CD8+ T cell during acute or chronic LCMV infection, we identified microRNAs that are specifically enriched in memory CD8+ T cells comparing to naive, effector or exhausted CD8+ T cells. MiR-150, a microRNA that has been shown to be important in multiple biological processes, was identified as a potential memory CD8+ T cell biased microRNA. Functional interrogation of the role of miR-150 demonstrated that absence of miR-150 in CD8+ T cells enhanced memory CD8+ T cell differentiation, by both increasing KLRG-CD127+ memory precursors population during effector phase and enhancing CD127+CXCR3+ central memory phenotype long-term. Overexpression of miR-150 in CD8+ T cells, in contrast, negatively regulated CD8+ T cell memory formation. Furthermore, we found that miR-150 KO CD8+ T cells had higher expression of c-Myb comparing to miR-150 WT CD8+ T cells, a result observed using both in vitro CD8+ T cell differentiation and following infection with LCMV-Armstrong in vivo . Gene expression analysis implicated a relationship between the level of c-Myb expression and CD8+ T cell memory formation through potential anti-apoptotic molecules such as bcl-2. Thus, our studies identify a key role for miR-150 in CD8+ T cell memory and implicate a mechanism of CD8+ T cell memory effect by this microRNA through regulation of c-Myb.