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Alliance"],"accepted":{"date-parts":[[2024,6,5]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:p>\n                    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-1\u03b1 subunit shapes an ILC phenotype upon acute colitis that contributes to intestinal damage. However, the impact of HIF signaling in NKp46\n                    <jats:sup>+<\/jats:sup>\n                    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-1\u03b1 isoform in NKp46+ ILCs show a decrease in NKp46\n                    <jats:sup>+<\/jats:sup>\n                    ILC1s but a concomitant rise in neutrophils and Ly6C\n                    <jats:sup>high<\/jats:sup>\n                    macrophages. Single-nucleus RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1\u03b1 KO mice and a loss of mucus-producing enterocytes and intestinal stem cells. This was, furthermore, associated with increased bone morphogenetic pathway\u2013integrin signaling, expansion of fibroblast subsets, and intestinal fibrosis. In summary, this suggests that HIF-1\u03b1\u2013mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202402593","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T15:15:15Z","timestamp":1718378115000},"page":"e202402593","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["The transcription factor HIF-1\u03b1 in NKp46+ ILCs limits chronic intestinal inflammation and fibrosis"],"prefix":"10.26508","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9689-6926","authenticated-orcid":true,"given":"Eric","family":"Nelius","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Anatomy, University of Zurich","place":[", Zurich, 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