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Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation.
Nat. Immunol. 15, 1079-1089 (2014)
Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (TFH cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the TH17 subset of helper T cells in the lungs. Roquin inhibited TH17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the TH17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IκBNS and IκBζ. This cooperation required binding of RNA by roquin and the nuclease activity of regnase-1. Upon recognition of antigen by the T cell antigen receptor (TCR), roquin and regnase-1 proteins were cleaved by the paracaspase MALT1. Thus, this pathway acts as a 'rheostat' by translating TCR signal strength via graded inactivation of post-transcriptional repressors and differential derepression of targets to enhance TH17 differentiation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Nf-kappa-b; Messenger-rna Decay; Helper T-cells; Transcription Factor; Pharmacological Inhibition; Protease Activity; Protects Mice; T-h-17 Cells; Activation; Autoimmunity
ISSN (print) / ISBN 1529-2908
Journal Nature Immunology
Quellenangaben Volume: 15, Issue: 11, Pages: 1079-1089
Publisher Nature Publishing Group
Publishing Place New York
Reviewing status Peer reviewed