Dataset Information

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

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.