Epigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2

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-gamma 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. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.