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

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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.

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Funding

This research was supported by key projects of the National Natural Science Foundation of China (NSFC) (NO:81630019), NSFC (NO: 81470986 and 81870519).

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Author notes

  1. Jing Chen and Changsheng Zhan contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People’s Republic of China

    Jing Chen, Changsheng Zhan, Li Zhang, Ligang Zhang, Yi Liu, Yong Zhang, Hexi Du, Chaozhao Liang & Xianguo Chen

  2. Institute of Urology, Anhui Medical University, Hefei, China

    Jing Chen, Changsheng Zhan, Li Zhang, Ligang Zhang, Yi Liu, Yong Zhang, Hexi Du, Chaozhao Liang & Xianguo Chen

  3. Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China

    Jing Chen, Changsheng Zhan, Li Zhang, Ligang Zhang, Yi Liu, Yong Zhang, Hexi Du, Chaozhao Liang & Xianguo Chen

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  1. Jing Chen
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Correspondence to Chaozhao Liang or Xianguo Chen.

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Chen, J., Zhan, C., Zhang, L. et al. The Hypermethylation of Foxp3 Promoter Impairs the Function of Treg Cells in EAP. Inflammation 42, 1705–1718 (2019). https://doi.org/10.1007/s10753-019-01030-0

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