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

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• 作者：Alvin Pratama¹ ; ⁵ ; Roybel R. Ramiscal¹ ; ⁵ ; Diego G. Silva¹ ; ⁵ ; Souvik K. Das¹ ; Vicki Athanasopoulos¹ ; Jessica Fitch¹ ; Natalia K. Botelho¹ ; Pheh-Ping Chang¹ ; Xin Hu¹ ; Jennifer J. Hogan¹ ; Paula Mañ ; a¹ ; David Bernal¹ ; Heinrich Korner⁴ ; Di Yu¹ ; Christopher C. Goodnow² ; Matthew C. Cook² ; ³ ; Carola G. Vinuesa¹ ; ^{carola.vinuesa@anu.edu.au}
• 刊名：Immunity
• 出版年：2013
• 出版时间：18 April, 2013
• 年：2013
• 卷：38
• 期：4
• 页码：669-680
• 全文大小：1927 K

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Summary

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-¦Ã (IFN-¦Ã) 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.