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

作者：Hu, Xiao; Zou, Yanli; Copland, David A.; Schewitz-Bowers, Lauren P.; Li, Yan; Lait, Philippa J. P.; Stimpson, Madeleine; Zhang, Zhihui; Guo, Shixin; Liang, Juanran; Chen, Tingting; Li, Jing Jing; Yuan, Sujing; Li, Shuo; Zhou, Penghui; Liu, Yizhi; Dick, Andrew D.; Wen, Xiaofeng^*; Lee, Richard W. J.^*; Wei, Lai^*

来源：EBioMedicine, 2022, 86: 104333.

DOI：10.1016/j.ebiom.2022.104333

• Th17
• IOX1
• Epigenetic drug
• 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.

• 单位
  南方医科大学; 中山大学