dc.contributor.author | Hewitson, JP | en_US |
dc.contributor.author | Shah, KM | en_US |
dc.contributor.author | Brown, N | en_US |
dc.contributor.author | Grevitt, P | en_US |
dc.contributor.author | Hain, S | en_US |
dc.contributor.author | Newling, K | en_US |
dc.contributor.author | Sharp, TV | en_US |
dc.contributor.author | Kaye, PM | en_US |
dc.contributor.author | Lagos, D | en_US |
dc.date.accessioned | 2019-03-21T10:43:06Z | |
dc.date.available | 2019-02-06 | en_US |
dc.date.issued | 2019-04 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/56389 | |
dc.description.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+ 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. | en_US |
dc.description.sponsorship | UK Medical Research Council through a New Investigator Research Grant (MR/L008505/1) | en_US |
dc.description.sponsorship | Programme Grant (G1000230) | en_US |
dc.description.sponsorship | Project Grant (MR/N009185/1) | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | EMBO Rep | en_US |
dc.subject | Leishmania | en_US |
dc.subject | Th cells | en_US |
dc.subject | miR‐132 | en_US |
dc.subject | microRNA | en_US |
dc.subject | ribosomal proteins | en_US |
dc.title | miR-132 suppresses transcription of ribosomal proteins to promote protective Th1 immunity. | en_US |
dc.type | Article | |
dc.rights.holder | (c) 2019 The Authors | |
dc.identifier.doi | 10.15252/embr.201846620 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30833344 | en_US |
pubs.issue | 4 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 20 | en_US |
dcterms.dateAccepted | 2019-02-06 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |