Hewitson, James Philip orcid.org/0000-0002-3265-6763, Shah, Kunal M, Brown, Najmeeyah et al. (6 more authors) (2019) miR-132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity. EMBO Reports. e46620. ISSN 1469-221X
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
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 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. |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 05 Mar 2019 13:50 |
Last Modified: | 05 Jan 2025 00:21 |
Published Version: | https://doi.org/10.15252/embr.201846620 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.15252/embr.201846620 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:143286 |
Download
Filename: Lagos_EMBOR_Author_Accepted_copy.pdf
Description: Lagos - EMBOR_Author_Accepted_copy