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

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JournalEMBO Reports
DateAccepted/In press - 6 Feb 2019
DateE-pub ahead of print - 4 Mar 2019
DatePublished (current) - 1 May 2019
Issue number4
Volume20
Early online date4/03/19
Original languageEnglish

Abstract

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 CD4+ T cell function is poorly understood. Here, we show that CD4+ 38 T cells express high levels of miR-132 and that T cell activation leads to miR-132 upregulation. The transcriptomic hallmark of splenic CD4+ 40 T cells lacking the miR 132/212 cluster during chronic infection is an increase in mRNAs levels of ribosomal protein (RP) genes. BTAF1, a co-factor of B-TFIID and novel miR132/212-3p target, and p300 contribute towards miR-132/212-mediated regulation of RP transcription. Following infection with Leishmania donovani miR-132-/- CD4+ T cells display enhanced expression of IL-10 and decreased IFNg. 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 CD4+ 50 T cell activation and protective immunity against pathogens

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© 2019 The Authors. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

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