| First Author | Krzywinska E | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 2 | PubMed ID | 35024767 |
| Mgi Jnum | J:319520 | Mgi Id | MGI:6864001 |
| Doi | 10.1084/jem.20210909 | Citation | Krzywinska E, et al. (2022) The transcription factor HIF-1alpha mediates plasticity of NKp46+ innate lymphoid cells in the gut. J Exp Med 219(2) |
| abstractText | 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)-gamma-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-1alpha isoform in NKp46+ ILCs show a decrease in IFN-gamma-expressing, T-bet+, NKp46+ ILC1s and a concomitant increase in IL-22-expressing, RORgammat+, NKp46+ ILC3s in the gut mucosa. Single-cell RNA sequencing revealed HIF-1alpha as a driver of ILC phenotypes, where HIF-1alpha promotes the ILC1 phenotype by direct up-regulation of T-bet. Loss of HIF-1alpha in NKp46+ cells prevents ILC3-to-ILC1 conversion, increases the expression of IL-22-inducible genes, and confers protection against intestinal damage. Taken together, our results suggest that HIF-1alpha shapes the ILC phenotype in the gut. |
