{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:39:58Z","timestamp":1772138398649,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Benaroya Research Institute"},{"name":"Gut Immunity Program at Benaroya Research Institute"},{"name":"Washington Research Foundation Post","award":["1T32GM136534"],"award-info":[{"award-number":["1T32GM136534"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-2140004"],"award-info":[{"award-number":["DGE-2140004"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01AI158624"],"award-info":[{"award-number":["R01AI158624"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Th2 cells must sense and adapt to the tissue milieu to provide protective host immunity and tissue repair. Here, we examined the mechanisms promoting Th2 cell differentiation and function within the small intestinal lamina propria. Single cell RNA-seq analyses of CD4+ T cells from the small intestinal lamina propria of helminth infected mice revealed high expression of the gene Epas1, encoding the transcription factor hypoxia-inducible factor 2a (HIF2\u03b1). In vitro, exposure to hypoxia or genetic HIF2\u03b1 activation promoted Th2 cell differentiation, even under non-polarizing conditions. In mice, HIF2\u03b1 activation in CD4+ T cells promoted intestinal Th2 cell accumulation in the absence of infection, and HIF2\u03b1-deficiency impaired CD4+ T cell-mediated host immunity to intestinal helminth infection. Our findings identified hypoxia, and the oxygen-regulated transcription factor Hypoxia-Inducible Factor 2\u03b1 (HIF2\u03b1), as key regulators of Th2 cell differentiation and function within the small intestine.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf138","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T19:44:27Z","timestamp":1752176667000},"page":"2543-2548","source":"Crossref","is-referenced-by-count":1,"title":["Hypoxia-inducible factor 2\u03b1 promotes protective Th2 cell responses during intestinal helminth infection"],"prefix":"10.1093","volume":"214","author":[{"given":"Jasmine C","family":"Labuda","sequence":"first","affiliation":[{"name":"Center for Fundamental Immunology, Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayla M","family":"Olsen","sequence":"additional","affiliation":[{"name":"Center for Fundamental Immunology, Benaroya Research Institute , Seattle, WA,","place":["United States"]},{"name":"Molecular and Cellular Biology Program, University of Washington , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheenam","family":"Verma","sequence":"additional","affiliation":[{"name":"Center for Fundamental Immunology, Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Kimmel","sequence":"additional","affiliation":[{"name":"Center for Fundamental Immunology, Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H","family":"Edwards","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology, Benaroya Research Institute , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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