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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
Immunity
Quellenangaben
Band: 38,
Heft: 4,
Seiten: 655-668
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed