Journal article
Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation
KM Jeltsch, D Hu, S Brenner, J Zöller, GA Heinz, D Nagel, KU Vogel, N Rehage, SC Warth, SL Edelmann, R Gloury, N Martin, C Lohs, M Lech, JE Stehklein, A Geerlof, E Kremmer, A Weber, HJ Anders, I Schmitz Show all
Nature Immunology | Published : 2014
DOI: 10.1038/ni.3008
Abstract
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 TH 17 subset of helper T cells in the lungs. Roquin inhibited TH 17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the TH 17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IκBNS and IκB. 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 ..
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Awarded by Boehringer Ingelheim Fonds
Funding Acknowledgements
We thank H.-M. Jack and J. Wittmann (Friedrich-Alexander-Universitat Erlangen, Germany) for the cloned 3' UTR of mouse Irf4; and D. Baumjohann for critical reading of the manuscript. Supported by the Deutsche Forschungsgemeinschaft (SFB 1054 TP-A03 and Z02 to V.H.; SFB 1054 TP-B01 to J.R.; SFB 1054 TP-A04 to D.K.; SFB 1054 TP-A02 to M.S.-S; GRK1202 to H.-J.A. and M.L.; SFB TR36 to M.H. and HO1116/5-2 to H.H.) the PCCC (M.H.), the Hofschneider Foundation (M.H.), Boehringer Ingelheim Fonds (G.A.H.) and The Federation of European Biochemical Societies (K.U.V.).