The DNA Methylation Inhibitor Zebularine Controls CD4+ T Cell Mediated Intraocular Inflammation

Yanli Zou, Xiao Hu, Lauren P Schewitz-Bowers, Madeleine L Stimpson, Li Miao, Xiaofei Ge, Liu Yang, Yan Li, Paul Bible, Xiaofeng Wen, Jing Jing Li, Yizhi Liu, Richard W J Lee, Lai Wei

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
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Abstract

CD4+ T cell mediated uveitis is conventionally treated with systemic immunosuppressive agents, including corticosteroids and biologics targeting key inflammatory cytokines. However, their long-term utility is limited due to various side effects. Here, we investigated whether DNA methylation inhibitor zebularine can target CD4+ T cells and control intraocular inflammation. Our results showed that zebularine restrained the expression of inflammatory cytokines IFN-γ and IL-17 in both human and murine CD4+ T cells in vitro. Importantly, it also significantly alleviated intraocular inflammation and retinal tissue damage in the murine experimental autoimmune uveitis (EAU) model in vivo, suggesting that the DNA methylation inhibitor zebularine is a candidate new therapeutic agent for uveitis.
Original languageEnglish
Article number1950
Number of pages12
JournalFrontiers in Immunology
Volume16
Issue number10
DOIs
Publication statusPublished - 16 Aug 2019

Keywords

  • uveitis
  • zebularine
  • DNA methylation inhibitor
  • CD4+ T cell
  • intraocular inflammation

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