STAT3 和 Smad3 在调节 Th17 细胞中 Tiam1 表达方面的相反功能。
Opposite functions of STAT3 and Smad3 in regulating Tiam1 expression in Th17 cells.
机构信息
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Translational Neurogenomics and Neuroinflammation, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Broad Institute at Harvard University and MIT, Boston, MA, USA.
出版信息
Small GTPases. 2020 Jan;11(1):62-68. doi: 10.1080/21541248.2017.1341365. Epub 2017 Sep 18.
We recently showed that Tiam1 expression is induced in pro-inflammatory T helper 17 (Th17) cells differentiated with interleukin (IL)-6 and TGF-β1, and together with Rac1 promote Th17 cell development and autoimmunity in a mouse model of multiple sclerosis. Here we found that STAT3 and Smad3, downstream transcription factors of IL-6 and TGF-β1, respectively, play opposing roles in regulating Tiam1 transcription in CD4 T-cells. While IL-6-STAT3 signaling promotes Tiam1 expression, TGF-β1-Smad3 induces the opposite outcome. At the Tiam1 promoter, both STAT3 and Smad3 bind to the Tiam1 promoter in Th17 cells. However, STAT3 induces Tiam1 promoter activity whereas Smad3 competes with STAT3 and inhibits its activity. Our findings uncover the complexity of STAT3/Smad3 signaling in regulating Tiam1 expression and Th17 cells.
我们最近发现，Tiam1 的表达在白细胞介素 (IL)-6 和转化生长因子 (TGF)-β1 诱导的促炎辅助性 T 细胞 17 (Th17) 细胞中被诱导，并且与 Rac1 一起促进多发性硬化症小鼠模型中的 Th17 细胞发育和自身免疫。在这里，我们发现 IL-6 和 TGF-β1 的下游转录因子 STAT3 和 Smad3 分别在 CD4 T 细胞中调节 Tiam1 转录中发挥相反的作用。虽然 IL-6-STAT3 信号促进 Tiam1 的表达，但 TGF-β1-Smad3 诱导相反的结果。在 Tiam1 启动子上，STAT3 和 Smad3 均结合在 Th17 细胞中的 Tiam1 启动子上。然而，STAT3 诱导 Tiam1 启动子活性，而 Smad3 与 STAT3 竞争并抑制其活性。我们的研究结果揭示了 STAT3/Smad3 信号在调节 Tiam1 表达和 Th17 细胞中的复杂性。
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