miR‐132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity

Determining the mechanisms that distinguish protective immunity from pathological chronic inflammation remains a fundamental challenge. miR‐132 has been shown to play largely immunoregulatory roles in immunity; however, its role in CD 4 + T cell function is poorly understood. Here, we show that CD 4 + T cells express high levels of miR‐132 and that T cell activation leads to miR‐132 up‐regulation. The transcriptomic hallmark of splenic CD 4 + T cells lacking the miR‐132/212 cluster during chronic infection is an increase in mRNA levels of ribosomal protein ( RP ) genes. BTAF 1, a co‐factor of B‐ TFIID and novel miR‐132/212‐3p target, and p300 contribute towards miR‐132/212‐mediated regulation of RP transcription. Following infection with Leishmania donovani, miR‐132 −/− CD 4 + T cells display enhanced expression of IL ‐10 and decreased IFN γ. This is associated with reduced hepatosplenomegaly and enhanced pathogen load. The enhanced IL ‐10 expression in miR‐132 −/− Th1 cells is recapitulated in vitro following treatment with phenylephrine, a drug reported to promote ribosome synthesis. Our results uncover that miR‐132/212‐mediated regulation of RP expression is critical for optimal CD 4 + T cell activation and protective immunity against pathogens.