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Trim33 mediates the proinflammatory function of Th17 cells.

ABSTRACT: Transforming growth factor-? (TGF-?) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-? signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.

SUBMITTER: Tanaka S

PROVIDER: S-EPMC6028517 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Trim33 mediates the proinflammatory function of Th17 cells.

Tanaka Shinya S Jiang Yu Y Martinez Gustavo J GJ Tanaka Kentaro K Yan Xiaowei X Kurosaki Tomohiro T Kaartinen Vesa V Feng Xin-Hua XH Tian Qiang Q Wang Xiaohu X Dong Chen C

The Journal of experimental medicine 20180621 7

Transforming growth factor-β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo<i>.</i> Trim33 was required for induction in vitro of Th17, but not T r ...[more]

PMID: 29930104

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Tripartite motif-containing 33 (Trim33) determines the pathogenic function of Th17 cells

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