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miR‐132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity
Author(s) -
Hewitson James P,
Shah Kunal M,
Brown Najmeeyah,
Grevitt Paul,
Hain Sofia,
Newling Katherine,
Sharp Tyson V,
Kaye Paul M,
Lagos Dimitris
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846620
Subject(s) - immunity , ribosomal protein , transcription (linguistics) , biology , transcription factor , microbiology and biotechnology , ribosomal rna , computational biology , genetics , gene , ribosome , immune system , rna , linguistics , philosophy
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.