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

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

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01950

DOI=10.3389/fimmu.2019.01950

ISSN=1664-3224

ABSTRACT=<p>CD4<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cells <italic>in vitro</italic>. Importantly, it also significantly alleviated intraocular inflammation and retinal tissue damage in the murine experimental autoimmune uveitis (EAU) model <italic>in vivo</italic>, suggesting that the DNA methylation inhibitor zebularine is a candidate new therapeutic agent for uveitis.</p>