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

doi:10.3389/fimmu.2019.01950

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

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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 language	English
Article number	1950
Number of pages	12
Journal	Frontiers in Immunology
Volume	16
Issue number	10
DOIs	https://doi.org/10.3389/fimmu.2019.01950
Publication status	Published - 16 Aug 2019

Keywords

uveitis
zebularine
DNA methylation inhibitor
CD4+ T cell
intraocular inflammation

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title = "The DNA Methylation Inhibitor Zebularine Controls CD4+ T Cell Mediated Intraocular Inflammation",

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.",

keywords = "uveitis, zebularine, DNA methylation inhibitor, CD4+ T cell, intraocular inflammation",

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

year = "2019",

month = aug,

day = "16",

doi = "10.3389/fimmu.2019.01950",

language = "English",

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T1 - The DNA Methylation Inhibitor Zebularine Controls CD4+ T Cell Mediated Intraocular Inflammation

AU - Zou, Yanli

AU - Hu, Xiao

AU - Schewitz-Bowers, Lauren P

AU - Stimpson, Madeleine L

AU - Miao, Li

AU - Ge, Xiaofei

AU - Yang, Liu

AU - Li, Yan

AU - Bible, Paul

AU - Wen, Xiaofeng

AU - Li, Jing Jing

AU - Liu, Yizhi

AU - Lee, Richard W J

AU - Wei, Lai

PY - 2019/8/16

Y1 - 2019/8/16

N2 - 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.

AB - 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.

KW - uveitis

KW - zebularine

KW - DNA methylation inhibitor

KW - CD4+ T cell

KW - intraocular inflammation

U2 - 10.3389/fimmu.2019.01950

DO - 10.3389/fimmu.2019.01950

M3 - Article (Academic Journal)

C2 - 31475011

SN - 1664-3224

VL - 16

JO - Frontiers in Immunology

JF - Frontiers in Immunology

IS - 10

M1 - 1950

ER -

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

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