biostudies-literatureBargiela DWellcome Trust1293723https://www.ebi.ac.uk/biostudies/studies/S-EPMC11058823biostudies-literatureUnknown15T cells must adapt to variations in tissue microenvironments; these adaptations include the degree of oxygen availability. The hypoxia-inducible factor (HIF) transcription factors control much of this adaptation, and thus regulate many aspects of T cell activation and function. The HIFs are in turn regulated by oxygen-dependent hydroxylases: both the prolyl hydroxylases (PHDs) which interact with the VHL tumour suppressor and control HIF turnover, and the asparaginyl hydroxylase known as the Factor inhibiting HIF (FIH), which modulates HIF transcriptional activity. To determine the role of this latter factor in T cell function, we generated T cell-specific FIH knockout mice. We found that FIH regulates T cell fate and function in a HIF-dependent manner and show that the effects of FIH actiFrontiers in immunologyThe factor inhibiting HIF regulates T cell differentiation and anti-tumour efficacy.PMC11058823211143/Z/18/ZJohnson RSVelica PBrice MKrause LCMCunha PPBarbieri LBargiela DGojkovic MRundqvist HFoskolou IPfalseThe factor inhibiting HIF regulates T cell differentiation and anti-tumour efficacy.T cells must adapt to variations in tissue microenvironments; these adaptations include the degree of oxygen availability. The hypoxia-inducible factor (HIF) transcription factors control much of this adaptation, and thus regulate many aspects of T cell activation and function. The HIFs are in turn regulated by oxygen-dependent hydroxylases: both the prolyl hydroxylases (PHDs) which interact with the VHL tumour suppressor and control HIF turnover, and the asparaginyl hydroxylase known as the Factor inhibiting HIF (FIH), which modulates HIF transcriptional activity. To determine the role of this latter factor in T cell function, we generated T cell-specific FIH knockout mice. We found that FIH regulates T cell fate and function in a HIF-dependent manner and show that the effects of FIH acti2024-01-01T00:00:00Z20242026-06-01T10:51:16.369Z2026-04-08T11:33:37.795ZS-EPMC110588233869026310.3389/fimmu.2024.1293723