HIF-1α regulates ADAM9 expression in Th17 cells during autoimmune disease

Hypoxia-inducible factor 1α (HIF-1α) promotes T helper 17 (Th17) differentiation, but whether it regulates ADAM9 expression in Th17 cells during autoimmune nephritis remains unclear. Hypoxia enhanced Th17 differentiation and increased ADAM9 expression in a HIF-1α-dependent manner. HIF-1α deficiency reduced ADAM9 expression and impaired Th17 differentiation in vitro. In anti-glomerular basement membrane nephritis and B6.lpr lupus-prone mice, T cell-specific HIF-1α deletion attenuated renal pathology and reduced kidney-infiltrating CD4⁺ and IL-17A-producing T cells. These findings identify ADAM9 as a HIF-1α-regulated target in Th17 cells that may contribute to autoimmune renal inflammation.