Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity.

ABSTRACT: Th17 cells are key drivers of autoimmune disease. However, the signaling pathways regulating Th17 polarization are poorly understood. Hedgehog signaling regulates cell fate decisions during embryogenesis and adult tissue patterning. Here we find that cell-autonomous Hedgehog signaling, independent of exogenous ligands, selectively drives the polarization of Th17 cells but not other T helper cell subsets. We show that endogenous Hedgehog ligand, Ihh, signals to activate both canonical and non-canonical Hedgehog pathways through Gli3 and AMPK. We demonstrate that Hedgehog pathway inhibition with either the clinically-approved small molecule inhibitor vismodegib or genetic ablation of Ihh in CD4⁺ T cells greatly diminishes disease severity in two mouse models of intestinal inflamma

SUBMITTER: Hanna J 

PROVIDER: S-EPMC9281293 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature