| First Author | Nelius E | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 9 | PubMed ID | 38876796 |
| Mgi Jnum | J:349918 | Mgi Id | MGI:7659932 |
| Doi | 10.26508/lsa.202402593 | Citation | Nelius E, et al. (2024) The transcription factor HIF-1alpha in NKp46+ ILCs limits chronic intestinal inflammation and fibrosis. Life Sci Alliance 7(9) |
| abstractText | Innate lymphoid cells (ILCs) are critical for intestinal adaptation to microenvironmental challenges, and the gut mucosa is characterized by low oxygen. Adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs), and the HIF-1alpha subunit shapes an ILC phenotype upon acute colitis that contributes to intestinal damage. However, the impact of HIF signaling in NKp46(+) ILCs in the context of repetitive mucosal damage and chronic inflammation, as it typically occurs during inflammatory bowel disease, is unknown. In chronic colitis, mice lacking the HIF-1alpha isoform in NKp46+ ILCs show a decrease in NKp46(+) ILC1s but a concomitant rise in neutrophils and Ly6C(high) macrophages. Single-nucleus RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1alpha KO mice and a loss of mucus-producing enterocytes and intestinal stem cells. This was, furthermore, associated with increased bone morphogenetic pathway-integrin signaling, expansion of fibroblast subsets, and intestinal fibrosis. In summary, this suggests that HIF-1alpha-mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage. |
