{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:19:10Z","timestamp":1785403150517,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,10]]},"group-title":"Immunology","reference-count":99,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 DK070855"],"award-info":[{"award-number":["R01 DK070855"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA231303"],"award-info":[{"award-number":["R01 CA231303"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P01 AI179406"],"award-info":[{"award-number":["P01 AI179406"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 AI007520"],"award-info":[{"award-number":["T32 AI007520"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["I-1874"],"award-info":[{"award-number":["I-1874"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>The intestinal microbiota shapes adaptive immunity, but the mechanisms remain incompletely defined. Here, we show that the microbiota initiates the movement of retinoids\u2014dietary vitamin A derivatives including retinol and retinoic acid\u2014through a sequential pathway from epithelial cells to myeloid cells and ultimately to T cells in the mesenteric lymph nodes (mLNs). This cellular axis is traversed over three days. Microbe-associated molecular patterns (MAMPs) initiate retinoid flux by inducing expression of serum amyloid A (SAA) proteins. These epithelial retinol-binding proteins are necessary and sufficient for epithelial-to-myeloid cell retinoid transfer and for myeloid cell migration to the mLNs. In the mLNs, microbial antigen drives retinoid transfer from myeloid cells to developing T cells, culminating in T cell retinoid uptake and transcriptional programming. This pathway is activated during postnatal development, when gut adaptive immunity is first established. These findings reveal that the microbiota programs intestinal adaptive immunity by regulating immune cell access to a nutrient-derived developmental signal.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>The gut microbiota enables vitamin A flux to developing intestinal CD4\u207a T cells.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Microbiota-induced SAA initiates vitamin A flux along a gut myeloid\u2013T cell axis.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Microbial molecular patterns and antigen drive distinct steps of vitamin A flux.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Microbiota-driven vitamin A flux programs intestinal T cell homing and maturation.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\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=\"674524v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.08.674524","type":"posted-content","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T13:45:13Z","timestamp":1757511913000},"source":"Crossref","is-referenced-by-count":1,"title":["The gut microbiota directs vitamin A flux to regulate intestinal T cell development"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2251-6561","authenticated-orcid":false,"given":"Tarun","family":"Srinivasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaitanya","family":"Dende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Ruhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie L.","family":"Moye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie 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