The Hypermethylation of Foxp3 Promoter Impairs the Function of Treg Cells in EAP

被引：27

作者：

Chen, Jing ^{[1
,2
,3
]}

Zhan, Changsheng ^{[1
,2
,3
]}

Zhang, Li ^{[1
,2
,3
]}

Zhang, Ligang ^{[1
,2
,3
]}

Liu, Yi ^{[1
,2
,3
]}

Zhang, Yong ^{[1
,2
,3
]}

Du, Hexi ^{[1
,2
,3
]}

Liang, Chaozhao ^{[1
,2
,3
]}

Chen, Xianguo ^{[1
,2
,3
]}

机构：

[1] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, Hefei 230022, Anhui, Peoples R China

[2] Anhui Med Univ, Inst Urol, Hefei, Anhui, Peoples R China

[3] Anhui Med Univ, Anhui Prov Key Lab Genitourinary Dis, Hefei, Anhui, Peoples R China

来源：

INFLAMMATION | 2019年 / 42卷 / 05期

基金：

中国国家自然科学基金;

关键词：

CP; CPPS; EAP; Treg cells; Foxp3; methylation; REGULATORY T-CELLS; PELVIC PAIN SYNDROME; AUTOIMMUNE PROSTATITIS; INFLAMMATION; MECHANISMS; EXPRESSION; MEDIATORS; MODEL; GLAND;

D O I：

10.1007/s10753-019-01030-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund's adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-gamma was increased, and TGF-beta was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-beta and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo. Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP.

引用

页码：1705 / 1718

页数：14

共 42 条

[1] Autoimmune prostatitis: Evidence of T cell reactivity with normal prostatic proteins [J].