The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1

Abstract

We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8⁺ T lymphocytes (CTL) generation and effector memory cell formation, is regulated in CTL by microRNA-155 (miR-155). Importantly, we show that the proliferative effect of miR-155 on CD8⁺ T cells is mediated by T-bet. T-bet levels in CTL were controlled <i>in vivo</i> by miR-155 <i>via</i> SH2 (Src homology 2)-containing inositol phosphatase-1 (SHIP-1), a known direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies reveal an important and unexpected signaling axis between miR-155, T-bet, and SHIP-1 in <i>in vivo</i> CTL responses and suggest an important signaling module that regulates effector CTL immunity.