{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:50Z","timestamp":1785412550265,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,10]]},"group-title":"Immunology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK070855"],"award-info":[{"award-number":["R01 DK070855"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL151650"],"award-info":[{"award-number":["R01 HL151650"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 AI005284"],"award-info":[{"award-number":["T32 AI005284"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["I-1874"],"award-info":[{"award-number":["I-1874"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Vitamin A is a central regulator of intestinal adaptive immunity, but its role in innate immunity is less defined. Antimicrobial proteins form a chemical barrier that protects the intestinal epithelium from microbial invasion. Among these, REG3 family lectins are induced by the microbiota, yet how nutritional cues intersect with microbial signals to control their expression remains unclear. Here, we show that dietary vitamin A promotes expression of REG3 antimicrobial lectins, including REG3G, in intestinal epithelial cells from both mice and humans. This induction is mediated by retinoic acid and requires retinoic acid receptor (RAR) signaling. Mechanistically, RARs bind directly to the\n                  <jats:italic>Reg3g<\/jats:italic>\n                  promoter adjacent to a STAT3 binding site. As STAT3 mediates microbiota-induced IL-22 signaling in epithelial cells, this arrangement provides a molecular framework for integrating nutritional and microbial inputs at the level of REG3G transcription. Extending these findings, we demonstrate that vitamin A\u2013retinoic acid signaling similarly promotes expression of \u03b1-defensin antimicrobial proteins. Together, these findings define a transcriptional mechanism by which vitamin A enhances epithelial antimicrobial defenses and strengthens mucosal innate immunity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"710399v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Vitamin A promotes epithelial expression of REG3 antimicrobial proteins in the intestine<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Retinoic acid receptors (RARs) directly activate mouse\n                        <jats:italic>Reg3g<\/jats:italic>\n                        and human\n                        <jats:italic>REG3G<\/jats:italic>\n                        transcription\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        RARs bind the\n                        <jats:italic>Reg3g<\/jats:italic>\n                        promoter adjacent to STAT3, integrating nutritional and microbial signals\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Vitamin A\u2013RAR signaling broadly regulates epithelial antimicrobial programs, including \u03b1-defensins<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.08.710399","type":"posted-content","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:30:11Z","timestamp":1773203411000},"source":"Crossref","is-referenced-by-count":0,"title":["Epithelial sensing of vitamin A shapes intestinal antimicrobial defense"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-8778","authenticated-orcid":false,"given":"Gabriella","family":"Quinn","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8665-0885","authenticated-orcid":false,"given":"Daniel C.","family":"Propheter","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gon\u00e7alo","family":"Vale","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8991-9413","authenticated-orcid":false,"given":"Ann","family":"Johnson","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hassell","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie L.","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 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