STAT3-mediated epigenetic silencing of FOXP3 in LADA T cells is regulated through HDAC5 and DNMT1

被引：19

作者：

Hou, Can ^{[1
,2
]}

Zhong, Yanjun ^{[1
,2
]}

Wang, Zhen ^{[3
,4
]}

Ming, Zhao

Huang, Gan ^{[3
,4
]}

Ouyang, Lin ^{[1
,2
]}

Li, Yijun ^{[3
,4
]}

Lu, Qianjin ^{[5
]}

Zhou, Zhiguang ^{[3
,4
]}

机构：

[1] Cent S Univ, Xiangya Hosp 2, Intens Care Unit, Changsha, Hunan, Peoples R China

[2] Cent S Univ, Diabet Ctr, Changsha, Hunan, Peoples R China

[3] Cent S Univ, Xiangya Hosp 2, Inst Metab & Endocrinol, Changsha, Hunan, Peoples R China

[4] Cent S Univ, Natl Clin Res Ctr Metab Dis, Key Lab Diabet Immunol, Minist Educ,Diabet Ctr,Metab Syndrome Res Ctr, Changsha, Hunan, Peoples R China

[5] Cent S Univ, Hunan Key Lab Med Epigen, Xiangya Hosp 2, Dept Dermatol, Changsha, Hunan, Peoples R China

来源：

CLINICAL IMMUNOLOGY | 2018年 / 191卷

基金：

中国国家自然科学基金; 国家教育部博士点专项基金资助;

关键词：

LADA; STAT3; HDAC5; DNMT1; FOXP3; DNA METHYLATION; TGF-BETA; AUTOIMMUNE-DISEASES; INDUCED EXPRESSION; CUTTING EDGE; IN-VIVO; LATENT; STAT3; GENE; DIFFERENTIATION;

D O I：

10.1016/j.clim.2017.12.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4(+) T cells, but the etiology remains unclear. Our study included in 20 LADA patients and 20 healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1, DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4+ T cells than controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3 acetylation at K9 and K14 of FOXP3 promoter were significantly lower than controls. Luciferase reporter assay showed that ectopic STAT3 expression significantly reduced FOXP3 promoter activities. The Foxp3 promoter was significantly hypermethylated in LADA than controls. LADA patients showed stronger binding of p-STAT3, HDAC5 and DNMT1 than controls using CHIP. These findings reveal a crucial role of STAT3 in regulating the epigenetic status of T cells in LADA. (C) 2017 Published by Elsevier Inc.

引用

页码：116 / 125

页数：10

共 58 条

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