ZEB1 promotes pathogenic Th1 and Th17 cell differentiation in multiple sclerosis.

ABSTRACT: Inappropriate CD4⁺ T helper (Th) differentiation can compromise host immunity or promote autoimmune disease. To identify disease-relevant regulators of T cell fate, we examined mutations that modify risk for multiple sclerosis (MS), a canonical organ-specific autoimmune disease. This analysis identified a role for Zinc finger E-box-binding homeobox (ZEB1). Deletion of ZEB1 protects against experimental autoimmune encephalitis (EAE), a mouse model of multiple sclerosis (MS). Mechanistically, ZEB1 in CD4⁺ T cells is required for pathogenic Th1 and Th17 differentiation. Genomic analyses of paired human and mouse expression data elucidated an unexpected role for ZEB1 in JAK-STAT signaling. ZEB1 inhibits miR-101-3p that represses JAK2 expression, STAT3/STAT4 phosphorylatio

SUBMITTER: Qian Y 

PROVIDER: S-EPMC8431781 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature