CD1d+ Goblet Cells Expand Colon-Resident Immature, Intermediate and Differentiated iNKT Cells to Limit Colitis

CD1d+ Goblet Cells Expand Colon-Resident Immature, Intermediate and Differentiated iNKT Cells to Limit Colitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article CD1d+ Goblet Cells Expand Colon-Resident Immature, Intermediate and Differentiated iNKT Cells to Limit Colitis Rodney Newberry, Vini John, Bibiana Barrios, Jacqueline Wang, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7603392/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Invariant Natural Killer T (iNKT) cells recognize glycolipid antigens presented on CD1d and rapidily respond to direct immune responses. iNKT cells develop in the thymus and migrate to peripheral tissues in what has been presumed to be differentiated/committed states. Accordingly, colonic iNKT cells are established in early life, considered to remain ‘fixed’ post-weaning, and determine life-long colitis susceptibility. Using single cell RNA sequencing (scRNA-seq), we demonstrate that humans and mice contain colonic iNKT populations transcriptionally resembling immature and intermediate thymic iNKT precursors. Contrary to prevailing paradigms, we demonstrate colonic iNKT cell populations expand in adult mice when CD1d expressing colonic goblet cells form goblet cell-associated antigen passages. Expansion preferentially affected intermediate iNKT cells, was durable, and protective in a colitis model. These studies reveal that the adult colon harbors iNKT cells with retained plasticity and uncover a novel role for goblet cells as unconventional antigen presenting cells regulating this axis. Biological sciences/Immunology/Mucosal immunology Biological sciences/Immunology/Lymphocytes/NK cells Full Text Additional Declarations Yes there is potential Competing Interest. Competing interests: R.D.N., K.G.M. and K.A.K. are inventors in patent US11,241,480 Methods for Modulation of Dietary and Microbial Exposure With Compounds Comprising An EGFR Ligand. All other authors declare no competing interests. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7603392","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":519567808,"identity":"61e0557d-aa8c-41df-9c62-32453c4bf8c3","order_by":0,"name":"Rodney 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