Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation

Katharina M. Jeltsch; Desheng Hu; Sven Brenner; Jessica Zöller; Gitta A. Heinz; Daniel Nagel; Katharina U. Vogel; Nina Rehage; Sebastian C. Warth; Stephanie L. Edelmann; Renee Gloury; Nina Martin; Claudia Lohs; Maciej Lech; Jenny E. Stehklein; Arie Geerlof; Elisabeth Kremmer; Achim Weber; Hans Joachim Anders; Ingo Schmitz; Marc Schmidt-Supprian; Mingui Fu; Helmut Holtmann; Daniel Krappmann; Jürgen Ruland; Axel Kallies; Mathias Heikenwalder; Vigo Heissmeyer

doi:10.1038/ni.3008

Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T_H17 differentiation

Katharina M. Jeltsch, Desheng Hu, Sven Brenner, Jessica Zöller, Gitta A. Heinz, Daniel Nagel, Katharina U. Vogel, Nina Rehage, Sebastian C. Warth, Stephanie L. Edelmann, Renee Gloury, Nina Martin, Claudia Lohs, Maciej Lech, Jenny E. Stehklein, Arie Geerlof, Elisabeth Kremmer, Achim Weber, Hans Joachim Anders, Ingo SchmitzMarc Schmidt-Supprian, Mingui Fu, Helmut Holtmann, Daniel Krappmann, Jürgen Ruland, Axel Kallies, Mathias Heikenwalder, Vigo Heissmeyer

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Abstract

Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (T_FH 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 T_H 17 subset of helper T cells in the lungs. Roquin inhibited T_H 17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the T_H 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 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 T_H 17 differentiation.

Original language	English
Pages (from-to)	1079-1089
Number of pages	11
Journal	Nature Immunology
Volume	15
Issue number	11
DOIs	https://doi.org/10.1038/ni.3008
State	Published - 25 Oct 2014
Externally published	Yes

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Jeltsch, K. M., 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., ... Heissmeyer, V. (2014). Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T_H17 differentiation. Nature Immunology, 15(11), 1079-1089. https://doi.org/10.1038/ni.3008

@article{02c49d8e9b3a4569af019d2471dad854,

title = "Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation",

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 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 TH 17 differentiation.",

author = "Jeltsch, {Katharina M.} and Desheng Hu and Sven Brenner and Jessica Z{\"o}ller and Heinz, {Gitta A.} and Daniel Nagel and Vogel, {Katharina U.} and Nina Rehage and Warth, {Sebastian C.} and Edelmann, {Stephanie L.} and Renee Gloury and Nina Martin and Claudia Lohs and Maciej Lech and Stehklein, {Jenny E.} and Arie Geerlof and Elisabeth Kremmer and Achim Weber and Anders, {Hans Joachim} and Ingo Schmitz and Marc Schmidt-Supprian and Mingui Fu and Helmut Holtmann and Daniel Krappmann and J{\"u}rgen Ruland and Axel Kallies and Mathias Heikenwalder and Vigo Heissmeyer",

year = "2014",

month = oct,

day = "25",

doi = "10.1038/ni.3008",

language = "English",

volume = "15",

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Jeltsch, KM, Hu, D, Brenner, S, Zöller, J, Heinz, GA, Nagel, D, Vogel, KU, Rehage, N, Warth, SC, Edelmann, SL, Gloury, R, Martin, N, Lohs, C, Lech, M, Stehklein, JE, Geerlof, A, Kremmer, E, Weber, A, Anders, HJ, Schmitz, I, Schmidt-Supprian, M, Fu, M, Holtmann, H, Krappmann, D, Ruland, J, Kallies, A, Heikenwalder, M & Heissmeyer, V 2014, 'Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T_H17 differentiation', Nature Immunology, vol. 15, no. 11, pp. 1079-1089. https://doi.org/10.1038/ni.3008

TY - JOUR

T1 - Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation

AU - Jeltsch, Katharina M.

AU - Hu, Desheng

AU - Brenner, Sven

AU - Zöller, Jessica

AU - Heinz, Gitta A.

AU - Nagel, Daniel

AU - Vogel, Katharina U.

AU - Rehage, Nina

AU - Warth, Sebastian C.

AU - Edelmann, Stephanie L.

AU - Gloury, Renee

AU - Martin, Nina

AU - Lohs, Claudia

AU - Lech, Maciej

AU - Stehklein, Jenny E.

AU - Geerlof, Arie

AU - Kremmer, Elisabeth

AU - Weber, Achim

AU - Anders, Hans Joachim

AU - Schmitz, Ingo

AU - Schmidt-Supprian, Marc

AU - Fu, Mingui

AU - Holtmann, Helmut

AU - Krappmann, Daniel

AU - Ruland, Jürgen

AU - Kallies, Axel

AU - Heikenwalder, Mathias

AU - Heissmeyer, Vigo

PY - 2014/10/25

Y1 - 2014/10/25

N2 - 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 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 TH 17 differentiation.

AB - 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 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 TH 17 differentiation.

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U2 - 10.1038/ni.3008

DO - 10.1038/ni.3008

M3 - Article

C2 - 25282160

AN - SCOPUS:84908209291

SN - 1529-2908

VL - 15

SP - 1079

EP - 1089

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T_H17 differentiation

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