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Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.<\/jats:p>","DOI":"10.1084\/jem.20210923","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T02:20:58Z","timestamp":1675304458000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":65,"title":["Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-7181","authenticated-orcid":true,"given":"Zhijuan","family":"Qiu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-9634","authenticated-orcid":true,"given":"Camille","family":"Khairallah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-3253","authenticated-orcid":true,"given":"Timothy H.","family":"Chu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1708-5680","authenticated-orcid":true,"given":"Jessica N.","family":"Imperato","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-6188","authenticated-orcid":true,"given":"Xinyuan","family":"Lei","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8160-636X","authenticated-orcid":true,"given":"Galina","family":"Romanov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-7230","authenticated-orcid":true,"given":"Amha","family":"Atakilit","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Lung Biology Center, Department of Medicine, University of California, San Francisco 2 , San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-9647","authenticated-orcid":true,"given":"Lynn","family":"Puddington","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Connecticut Health 3 , Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-5888","authenticated-orcid":true,"given":"Brian S.","family":"Sheridan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University 1 , Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"2023022114223922200_","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.4049\/jimmunol.1201945","article-title":"Critical role for all-trans retinoic acid for optimal effector and effector memory CD8 T cell differentiation","volume":"190","author":"Allie","year":"2013","journal-title":"J. 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