{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:29:23Z","timestamp":1791325763204,"version":"4.3.1"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"85","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,7,28]]},"abstract":"<jats:p>\n            Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell activation culminates in intraepithelial T cell (T-IEL)\u2013mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4\n            <jats:sup>+<\/jats:sup>\n            follicular T helper (T\n            <jats:sub>FH<\/jats:sub>\n            ) cells, regulatory T cells (T\n            <jats:sub>regs<\/jats:sub>\n            ), and natural CD8\n            <jats:sup>+<\/jats:sup>\n            \u03b1\u03b2 and \u03b3\u03b4 T-IELs. Natural CD8\n            <jats:sup>+<\/jats:sup>\n            \u03b1\u03b2 and \u03b3\u03b4 T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both \u03b1\u03b2 and \u03b3\u03b4 T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells after gluten ingestion.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adf4312","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T17:58:37Z","timestamp":1689357517000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":52,"title":["Gluten induces rapid reprogramming of natural memory \u03b1\u03b2 and \u03b3\u03b4 intraepithelial T cells to induce cytotoxicity in celiac disease"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-9699","authenticated-orcid":true,"given":"Adam","family":"Kornberg","sequence":"first","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Microbiology and Immunology, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-2491","authenticated-orcid":true,"given":"Theo","family":"Botella","sequence":"additional","affiliation":[{"name":"Columbia Center for Human Development, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Genetics and Development, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8717-2435","authenticated-orcid":true,"given":"Christine S.","family":"Moon","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Columbia Center for Human Development, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Genetics and Development, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4155-7158","authenticated-orcid":true,"given":"Samhita","family":"Rao","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Microbiology and Immunology, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8575-3155","authenticated-orcid":true,"given":"Jared","family":"Gelbs","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Pediatrics, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Columbia Center for Human Development, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Genetics and Development, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-5453","authenticated-orcid":true,"given":"Jonathan","family":"Miller","sequence":"additional","affiliation":[{"name":"Columbia Center for Human Development, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Genetics and Development, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Bacarella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-5069","authenticated-orcid":true,"given":"Javier A.","family":"Garc\u00eda-Vilas","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Microbiology and Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5123-9904","authenticated-orcid":true,"given":"Justin","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-1418","authenticated-orcid":true,"given":"Xuechen","family":"Yu","sequence":"additional","affiliation":[{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8111-6780","authenticated-orcid":true,"given":"Izabela","family":"Krupska","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-2321","authenticated-orcid":true,"given":"Erin","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8970-8544","authenticated-orcid":true,"given":"Reuben","family":"Garcia-Carrasquillo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lebwohl","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneeta","family":"Krishnareddy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-4499","authenticated-orcid":true,"given":"Suzanne","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-9634","authenticated-orcid":true,"given":"Peter H.\u00a0R.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6250-048X","authenticated-orcid":true,"given":"Govind","family":"Bhagat","sequence":"additional","affiliation":[{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Pathology and Cell Biology, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-7261","authenticated-orcid":true,"given":"Kelley S.","family":"Yan","sequence":"additional","affiliation":[{"name":"Columbia Center for Human Development, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Genetics and Development, Columbia University, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2667-5335","authenticated-orcid":true,"given":"Arnold","family":"Han","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Microbiology and Immunology, Columbia University, New\u00a0York, NY, USA."},{"name":"Department of Medicine, Digestive and Liver Diseases, Columbia University, New\u00a0York, NY, USA."},{"name":"Celiac Disease Center, Columbia University, New\u00a0York, NY, 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