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

Autor: Hewitson JP; Centre for Immunology and Infection and York Biomedical Research Institute, Hull York Medical School and Department of Biology, University of York, York, UK., Shah KM; Centre of Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University London, London, UK., Brown N; Centre for Immunology and Infection and York Biomedical Research Institute, Hull York Medical School and Department of Biology, University of York, York, UK., Grevitt P; Centre of Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University London, London, UK., Hain S; Centre for Immunology and Infection and York Biomedical Research Institute, Hull York Medical School and Department of Biology, University of York, York, UK., Newling K; Genomics and Bioinformatics Laboratory, Bioscience Technology Facility, Department of Biology, University of York, York, UK., Sharp TV; Centre of Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University London, London, UK., Kaye PM; Centre for Immunology and Infection and York Biomedical Research Institute, Hull York Medical School and Department of Biology, University of York, York, UK., Lagos D; Centre for Immunology and Infection and York Biomedical Research Institute, Hull York Medical School and Department of Biology, University of York, York, UK dimitris.lagos@york.ac.uk.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2019 Apr; Vol. 20 (4). Date of Electronic Publication: 2019 Mar 04.
DOI: 10.15252/embr.201846620
Abstrakt: 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 + T cells express high levels of miR-132 and that T cell activation leads to miR-132 up-regulation. The transcriptomic hallmark of splenic CD4 + T cells lacking the miR-132/212 cluster during chronic infection is an increase in mRNA levels of ribosomal protein (RP) genes. BTAF1, 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 -/- CD4 + T cells display enhanced expression of IL-10 and decreased IFNγ. 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 + T cell activation and protective immunity against pathogens.
(© 2019 The Authors.)
Databáze: MEDLINE
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