biostudies-literatureKrzywinska ESwiss National FundSwiss National Centre for Competence in Research “Kidney.CH”University of ZurichSwiss Cancer Leaguee20210909https://www.ebi.ac.uk/biostudies/studies/S-EPMC8763886biostudies-literatureUnknown219(2)Gut innate lymphoid cells (ILCs) show remarkable phenotypic diversity, yet microenvironmental factors that drive this plasticity are incompletely understood. The balance between NKp46+, IL-22-producing, group 3 ILCs (ILC3s) and interferon (IFN)-γ-producing group 1 ILCs (ILC1s) contributes to gut homeostasis. The gut mucosa is characterized by physiological hypoxia, and adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs). However, the impact of HIFs on ILC phenotype and gut homeostasis is not well understood. Mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in IFN-γ-expressing, T-bet+, NKp46+ ILC1s and a concomitant increase in IL-22-expressing, RORγt+, NKp46+ ILC3s in the gut mucosa. Single-cell RNA sequencing revealed HIF-1α as a driver of The Journal of experimental medicineThe transcription factor HIF-1α mediates plasticity of NKp46+ innate lymphoid cells in the gut.PMC8763886KFS-4398-02-2018KFS-5402-08-2021N-403-06-26 HCP310030_179235Nagarajan SKrzywinska EFandrey JGotthardt DKerdiles YMZacharjasz JTambuwala MMPeyssonnaux CCummins ESexl VTaylor CTSobecki MPelletier AStockmann CfalseThe transcription factor HIF-1α mediates plasticity of NKp46+ innate lymphoid cells in the gut.Gut innate lymphoid cells (ILCs) show remarkable phenotypic diversity, yet microenvironmental factors that drive this plasticity are incompletely understood. The balance between NKp46+, IL-22-producing, group 3 ILCs (ILC3s) and interferon (IFN)-γ-producing group 1 ILCs (ILC1s) contributes to gut homeostasis. The gut mucosa is characterized by physiological hypoxia, and adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs). However, the impact of HIFs on ILC phenotype and gut homeostasis is not well understood. Mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in IFN-γ-expressing, T-bet+, NKp46+ ILC1s and a concomitant increase in IL-22-expressing, RORγt+, NKp46+ ILC3s in the gut mucosa. Single-cell RNA sequencing revealed HIF-1α as a driver of 2022-01-01T00:00:00Z2022 Feb2025-04-05T09:00:37.128Z2025-04-05T09:00:37.128ZS-EPMC87638863502476710.1084/jem.20210909