HIF1α-glycolysis engages activation-induced cell death to drive IFN-γ induction in hypoxic T cells.

ABSTRACT: The role of HIF1α-glycolysis in regulating IFN-γ induction in hypoxic T cells is unknown. Given that hypoxia is a common feature in a wide array of pathophysiological contexts such as tumor and that IFN-γ is instrumental for protective immunity, it is of great significance to gain a clear idea on this. Combining pharmacological and genetic gain-of-function and loss-of-function approaches, we find that HIF1α-glycolysis 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 significantly abrogate IFN-γ induction. Conversely, HIF1α stabilization in T cells by hypoxia and VHL deletion (VHL^-/-) promotes IFN-γ production. Mechanistically, reduced IFN-γ production in hypoxic

SUBMITTER: Shen H 

PROVIDER: S-EPMC10802708 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature