T cell-specific HIF-2α attenuates colitis by antagonizing notch-driven Th2 differentiations

Our results establish a non-redundant protective function for T cell-intrinsic HIF-2α in ulcerative colitis. The protein directly engages Notch1-NICD to restrain Notch signal transduction, ultimately limiting pathological Th2 cell differentiation and ameliorating intestinal inflammation. These data reconcile prior contradictory findings by revealing a crucial cellular context-dependent mechanism.