Hu, Xiao;
Zou, Yanli;
Copland, David A;
Schewitz-Bowers, Lauren P;
Li, Yan;
Lait, Philippa JP;
Stimpson, Madeleine;
... Wei, Lai; + view all
(2022)
Epigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2.
EBioMedicine
, 86
, Article 104333. 10.1016/j.ebiom.2022.104333.
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Abstract
BACKGROUND: Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases. METHODS: Using an in vitro culture system, we screened an epigenetics compound library for inhibitors of IFN-γ and IL-17 expression in murine Th1 and Th17 cultures. FINDINGS: This identified IOX1 as an effective suppressor of IL-17 expression in both murine and human CD4+ T cells. Furthermore, we found that IOX1 suppresses Il17a expression directly by targeting TET2 activity on its promoter in Th17 cells. Using established pre-clinical models of intraocular inflammation, treatment with IOX1 in vivo reduced the migration/infiltration of Th17 cells into the site of inflammation and tissue damage. INTERPRETATION: These results provide evidence of the strong potential for IOX1 as a viable therapy for inflammatory diseases, in particular of the eye. FUNDING: This study was supported by the National Key Research and Development Program of China 2021YFA1101200 (2021YFA1101204) to LW and XW; the National Natural Science Foundation of China 81900844 to XH and 82171041 to LW; the China Postdoctoral Science Foundation 2021M700776 and the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine 20221373 to YZ; and the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS (National Health Service) Foundation Trust and University College London Institute of Ophthalmology, UK (DAC, LPS, PJPL, MS, ADD and RWJL). The views expressed are those of the authors and not necessarily those of the NIHR or the UK's Department of Health and Social Care.
| Type: | Article |
|---|---|
| Title: | Epigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2 |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2022.104333 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2022.104333 |
| Language: | English |
| Additional information: | © 2022 The Author(s). Published by Elsevier B.V. Under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Epigenetic drug, IOX1, TET2, Th17 |
| 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.ucl.ac.uk/id/eprint/10159034 |
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