HIF1α-regulated glycolysis promotes activation-induced cell death and IFN-γ induction in hypoxic T cells.

ABSTRACT: Hypoxia is a common feature in various pathophysiological contexts, including tumor microenvironment, and IFN-γ is instrumental for anti-tumor immunity. HIF1α has long been known as a primary regulator of cellular adaptive responses to hypoxia, but its role in IFN-γ induction in hypoxic T cells is unknown. Here, we show that the HIF1α-glycolysis axis controls IFN-γ induction in both human and mouse T cells, activated under hypoxia. Specific deletion of HIF1α in T cells (Hif1α^-/-) and glycolytic inhibition suppresses IFN-γ induction. Conversely, HIF1α stabilization by hypoxia and VHL deletion in T cells (Vhl^-/-) increases IFN-γ production. Hypoxic Hif1α^-/- T cells are less able to kill tumor cells in vitro, and tumor-bearing Hif1α^-/- mice are not

SUBMITTER: Shen H 

PROVIDER: S-EPMC11526104 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature