Foxp3+CD4+ regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells. The CD3+T cell and Foxp3+CD4+ regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry. However, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein–protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b–MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP). Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function.

中文翻译：

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MKL-1 是 STAT5b 的共激活剂，STAT5b 是 Treg 细胞发育和功能的调节剂。

Foxp3+CD4+ 调节性 T 细胞 (Treg) 是自身免疫性疾病的关键事件。STAT5b 是 IL-2/15 和 FOXP3（Treg 细胞的主调节器）之间的关键链接。CD3+T 细胞和 Foxp3+CD4+ 调节性 T 细胞过表达或敲低 MKL-1 和 STAT5a，并测试 Treg 细胞的发育和功能。MKL-1 和 STAT5a 的直接相互作用通过共免疫沉淀试验、荧光素酶试验、免疫荧光染色和酵母双杂交筛选进行分析。通过qPCR和蛋白质印迹和流式细胞术分析MKL-1和STAT5a对Treg基因表达的影响。然而，在自身免疫性疾病中介导 STAT5b 依赖性 Treg 基因表达和 Treg 细胞表型和功能的分子机制尚未明确。这里，我们报告 MKL-1 是主要 Treg 基因转录因子 STAT5b 的共激活剂，这是人类 Treg 细胞表型和功能所必需的。STAT5b 的 N 端包含一个基本的卷曲螺旋蛋白-蛋白相互作用域，结合 MKL-1 的 C 端激活域并增强 MKL-1 介导的 Treg 特异性、含有 CArG 的启动子的转录激活，包括 Treg -特定基因 Foxp3。通过特定的小干扰 RNA 抑制内源性 STAT5b 表达减弱了培养的人类细胞中的 MKL-1 转录激活。STAT5b-MKL-1 相互作用确定了 Treg 特异性基因调控和调控小鼠 Treg 细胞发育和功能的作用，并提出了自身免疫性疾病特发性血小板减少性紫癜 (ITP) 保护作用的可能机制。