Zou, Y;
Hu, X;
Schewitz-Bowers, LP;
Stimpson, M;
Miao, L;
Ge, X;
Yang, L;
... Wei, L; + view all
(2019)
The DNA Methylation Inhibitor Zebularine Controls CD4(+) T Cell Mediated Intraocular Inflammation.
Frontiers In Immunology
, 10
, Article 1950. 10.3389/fimmu.2019.01950.
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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.
| Type: | Article |
|---|---|
| Title: | The DNA Methylation Inhibitor Zebularine Controls CD4(+) T Cell Mediated Intraocular Inflammation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2019.01950 |
| Publisher version: | https://doi.org/10.3389/fimmu.2019.01950 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | uveitis, zebularine, DNA methylation inhibitor, CD4+ T cell, intraocular inflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10114643 |
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