MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function
Posted on 2020-07-10 - 04:26
Abstract Background 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. Methods 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. Results 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). Conclusions Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. Video abstract
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Xiang, Yuan; Wang, Jun; Li, Jia Peng; Guo, Wei; Huang, Feng; Zhang, Hui Min; et al. (2020). MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5055396.v1
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AUTHORS (15)
YX
Yuan Xiang
JW
Jun Wang
JL
Jia Peng Li
WG
Wei Guo
FH
Feng Huang
HZ
Hui Min Zhang
HL
Han Han Li
ZD
Zhou Tong Dai
ZZ
Zi Jian Zhang
HL
Hui Li
LB
Le Yuan Bao
CG
Chao Jiang Gu
KC
Kun Chen
TZ
Tong Cun Zhang
XL
Xing Hua Liao