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

Abstract:

: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-γ was increased, and TGF-β 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-β 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.

journal_name

Inflammation

journal_title

Inflammation

authors

Chen J,Zhan C,Zhang L,Zhang L,Liu Y,Zhang Y,Du H,Liang C,Chen X

doi

10.1007/s10753-019-01030-0

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1705-1718

issue

5

eissn

0360-3997

issn

1573-2576

pii

10.1007/s10753-019-01030-0

journal_volume

42

pub_type

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