Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People's Republic of China.
Institute of Urology, Anhui Medical University, Hefei, China.
Inflammation. 2019 Oct;42(5):1705-1718. doi: 10.1007/s10753-019-01030-0.
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.
调节性 T 细胞（Treg 细胞）对于维持 CP/CPPS 中的免疫稳态至关重要，但调节 Treg 细胞功能的分子机制仍不清楚。本研究的主要目的是探讨实验性自身免疫性前列腺炎（EAP）小鼠模型中 Treg 细胞免疫抑制功能与 Foxp3 启动子甲基化水平之间的关系。通过向 NOD 小鼠皮下注射前列腺类固醇结合蛋白（PSBP）和完全弗氏佐剂来诱导 EAP 模型。组织学分析显示 EAP 模型成功诱导。EAP 模型血清中 IFN-γ表达增加，TGF-β表达降低。EAP 模型脾脏淋巴细胞中 Treg 细胞的比例增加。EAP 中 Tregs 的抑制能力受损。Foxp3 启动子的甲基化水平增加，Foxp3 的表达减少。向 EAP 小鼠注射 DNA 甲基化抑制剂 AZA 后，前列腺炎症减轻，TGF-β和 Foxp3 的表达增加，Tregs 的抑制功能在体外和体内得到改善。因此，我们得出结论，Treg 细胞中 Foxp3 启动子的异常高甲基化导致 Treg 细胞的抑制功能受损，从而加剧 EAP 中的自身免疫性炎症损伤。
