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Jeltsch, K. ; Hu, D. ; Brenner, S. ; Zöller, J. ; Heinz, G.A. ; Nagel, D. ; Vogel, K.U. ; Rehage, N. ; Warth, S.C. ; Edelmann, S.L. ; Gloury, R.* ; Martin, N. ; Lohs, C. ; Lech, M.* ; Stehklein, J.E. ; Geerlof, A. ; Kremmer, E. ; Weber, A.* ; Anders, H.J.* ; Schmitz, I.* ; Schmidt-Supprian, M.* ; Fu, M.* ; Holtmann, H.* ; Krappmann, D. ; Ruland, J.* ; Kallies, A.* ; Heikenwälder, M. ; Heissmeyer, V.

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)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 15, Heft: 11, Seiten: 1079-1089 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
Institute of Virology (VIRO)
Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOX)
Institute of Structural Biology (STB)