biostudies-literatureHu XNational Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL InstitNational Institute for Health Research (NIHR)National Natural Science Foundation of ChinaChina Postdoctoral Science FoundationNational Institute for Health and Care ResearchNational Key Research and Development Program of China104333https://www.ebi.ac.uk/biostudies/studies/S-EPMC9646865biostudies-literatureUnknown86<h4>Background</h4>Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>These results provide evEBioMedicineEpigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2.PMC96468652021M70077620221373821710412021YFA1101200819008442021YFA1101204Yuan SWen XLait PJPLee RWJCopland DAZhou PHu XStimpson MGuo SSchewitz-Bowers LPDick ADZou YLiu YLi YLi SZhang ZLiang JLi JJWei LChen TfalseEpigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2.<h4>Background</h4>Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>These results provide ev2022-01-01T00:00:00Z2022 Nov2025-04-05T12:31:36.473Z2024-11-05T22:00:33.709ZS-EPMC96468653633566510.1016/j.ebiom.2022.104333