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Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation

Citation

Pratama, A and Ramiscal, RR and Silva, DG and Das, SK and Athanasopoulos, V and Fitch, J and Botelho, NK and Chang, PP and Hu, X and Hogan, JJ and Mana, P and Bernal, D and Korner, H and Yu, D and Goodnow, CC and Cook, MC and Vinuesa, CG, Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation, Immunity, 38, (4) pp. 669-680. ISSN 1074-7613 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Elsevier Inc.

DOI: doi:10.1016/j.immuni.2013.01.011

Abstract

Accumulation of T follicular helper (Tfh) cells and proinflammatory cytokines drive autoantibody-mediated diseases. The RNA-binding protein Roquin-1 (Rc3h1) represses the inducible costimulator ICOS and interferon-γ (IFN-γ) in T cells to prevent Tfh cell accumulation. Unlike Rc3h1 san mice with a mutation in the ROQ domain of Roquin-1, mice lacking the protein, paradoxically do not display increased Tfh cells. Here we have analyzed mice with mutations that eliminate the RING domain from Roquin-1 or its paralog, Roquin-2 (Rc3h2). RING or ROQ mutations both disrupted Icos mRNA regulation by Roquin-1, but, unlike the ROQ mutant that still occupied mRNA-regulating stress granules, RING-deficient Roquin-1 failed to localize to stress granules and allowed Roquin-2 to compensate in the repression of ICOS and Tfh cells. These paralogs also targeted tumor necrosis factor (TNF) in nonlymphoid cells, ameliorating autoantibody-induced arthritis. The Roquin family emerges as a posttranscriptional brake in the adaptive and innate phases of antibody responses. © 2013 Elsevier Inc. All rights reserved.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Korner, H (Professor Heinrich Korner)
ID Code:84408
Year Published:2013
Web of Science® Times Cited:65
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-05-14
Last Modified:2017-11-07
Downloads:0

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