Trim33 介导 Th17 细胞的促炎功能。

Trim33 mediates the proinflammatory function of Th17 cells.

机构信息

Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX.

Division of Immunology and Genome Biology, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

出版信息

J Exp Med. 2018 Jul 2;215(7):1853-1868. doi: 10.1084/jem.20170779. Epub 2018 Jun 21.

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 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 and 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.

转化生长因子-β（TGF-β）调节调节性 T 细胞（Treg）和辅助性 T 细胞 17（Th17）的分化，但其作用机制尚不清楚。在这里，我们报告三结构域蛋白 33（Trim33），一种与 Smad2 相关的 TGF-β信号转导调节剂，调节 Th17 细胞的促炎功能。T 细胞中 Trim33 的缺失减轻了体内的自身免疫性疾病。Trim33 是体外诱导 Th17 而不是 Treg 细胞所必需的。此外，Smad4 和 Trim33 在调节 IL-10 表达中发挥相反的作用；Trim33 的缺失增强了 IL-10 的产生。此外，Trim33 被招募到和基因座，依赖于 Smad2，并在 Th17 分化过程中介导它们的染色质重塑。因此，Trim33 通过诱导 IL-17 和抑制 IL-10 表达来促进 Th17 细胞的促炎功能。