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Immunol."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    Group 2 innate lymphoid cells (ILC2s) support tissue homeostasis and type 2 inflammation. ILC2s, which are found in many tissues, adapt to local cues to perform tissue-specific functions. Intestinal ILC2s rapidly respond to helminth and protozoan infections via cross-talk with tuft cells, but the mechanism guiding this adaptation remains unclear. Here, we identify Notch signaling, triggered by the ligand Delta-like 1 on goblet cells, as a key regulator of gut ILC2 specialization in mice. Loss of the Notch signaling protein RBPJ did not impair ILC2 development but altered the expression of interleukin-33 (IL-33) and IL-25 receptors (ST2 and IL-17RB, respectively) on gut ILC2s. This increased sensitivity to IL-33, promoted IL-5 and IL-13 production, and drove the expansion of gut eosinophils and goblet cells. Moreover, RBPJ-deficient ILC2s failed to respond to tuft cell\u2013derived IL-25 after\n                    <jats:italic toggle=\"yes\">Tritrichomonas musculis<\/jats:italic>\n                    colonization. Thus, RBPJ-dependent Notch responsiveness in ILC2s regulates intestinal tissue adaptation and primes the tuft cell\u2013ILC2 circuit for intestinal homeostasis.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adu1870","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:59:11Z","timestamp":1778867951000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Goblet cells tune ILC2 activity through a gut-specific response checkpoint"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-3512","authenticated-orcid":true,"given":"Kyle","family":"Burrows","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, ON, Canada."},{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6835-1961","authenticated-orcid":true,"given":"Louis","family":"Ngai","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, ON, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0773-8994","authenticated-orcid":true,"given":"Siu Ling","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, ON, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-1469","authenticated-orcid":true,"given":"Pailin","family":"Chiaranunt","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, ON, Canada."},{"name":"Department of Laboratory Medicine, Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7197-2243","authenticated-orcid":true,"given":"Edward L. 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