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Open Access Green as soon as Postprint is submitted to ZB.
Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation.
Immunity 38, 655-668 (2013)
The Roquin-1 protein binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. A single point mutation in Roquin-1, but not gene ablation, increases follicular helper T (Tfh) cell numbers and causes lupus-like autoimmune disease in mice. In T cells, we did not identify a unique role for the much lower expressed paralog Roquin-2. However, combined ablation of both genes induced accumulation of T cells with an effector and follicular helper phenotype. We showed that Roquin-1 and Roquin-2 proteins redundantly repressed the mRNA of inducible costimulator (Icos) and identified the Ox40 costimulatory receptor as another shared mRNA target. Combined acute deletion increased Ox40 signaling, as well as Irf4 expression, and imposed Tfh differentiation on CD4+ T cells. These data imply that both proteins maintain tolerance by preventing inappropriate T cell activation and Tfh cell differentiation, and that Roquin-2 compensates in the absence of Roquin-1, but not in the presence of its mutated form.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Transcription Factor Irf4; B-cells; Kappa-b; Phosphoinositide 3-kinase; Systemic Autoimmunity; Expression; Protein; Generation; Leads; Bcl6
ISSN (print) / ISBN
1074-7613
e-ISSN
1097-4180
Journal
Immunity
Quellenangaben
Volume: 38,
Issue: 4,
Pages: 655-668
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed