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Here, we showed that at steady-state LIGHT, an HVEM ligand, binding to epithelial HVEM promoted the survival of small intestine IETs. RNA-seq and addition of HVEM ligands to epithelial organoids indicated that HVEM increased epithelial synthesis of basement membrane proteins, including collagen IV, which bound to \u03b2<jats:sub>1<\/jats:sub>integrins expressed by IETs. Therefore, we proposed that IET survival depended on \u03b2<jats:sub>1<\/jats:sub>integrin binding to collagen IV and showed that \u03b2<jats:sub>1<\/jats:sub>integrin\u2013collagen IV interactions supported IET survival in vitro. Moreover, the absence of \u03b2<jats:sub>1<\/jats:sub>integrin expression by T lymphocytes decreased TCR \u03b1\u03b2<jats:sup>+<\/jats:sup>IETs in vivo. Intravital microscopy showed that the patrolling movement of IETs was reduced without epithelial HVEM. As likely consequences of decreased number and movement, protective responses to<jats:italic>Salmonella enterica<\/jats:italic>were reduced in mice lacking either epithelial HVEM, HVEM ligands, or \u03b2<jats:sub>1<\/jats:sub>integrins. Therefore, IETs, at steady state and after infection, depended on HVEM expressed by epithelial cells for the synthesis of collagen IV by epithelial cells. Collagen IV engaged \u03b2<jats:sub>1<\/jats:sub>integrins on IETs that were important for their maintenance and for their protective function in mucosal immunity.<\/jats:p>","DOI":"10.1126\/sciimmunol.abm6931","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T17:57:38Z","timestamp":1659117458000},"source":"Crossref","is-referenced-by-count":32,"title":["Epithelial HVEM maintains intraepithelial T cell survival and contributes to host protection"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-724X","authenticated-orcid":true,"given":"Goo-Young","family":"Seo","sequence":"first","affiliation":[{"name":"La Jolla Institute for Immunology, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8624-1160","authenticated-orcid":true,"given":"Daisuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology, La 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