{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:27:47Z","timestamp":1791098867173,"version":"4.1.0"},"reference-count":49,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2,16]]},"abstract":"<jats:p>Extrathymic induction of regulatory T (T reg) cells is essential to the regulation of effector T cell responses in the periphery. In addition to Foxp3, T reg cell expression of suppressive cytokines, such as IL-10, is essential for peripheral tolerance, particularly in the intestines. TGF-\u03b2 has been shown to induce expression of Foxp3 as well as IL10 and the vitamin A metabolite; all-trans retinoic acid (RA [at-RA]) has been found to enhance the former. We report that in contrast to its enhancement of TGF-\u03b2\u2013mediated Foxp3 induction, at-RA potently inhibits the TGF-\u03b2\u2013mediated induction of Il10 in naive CD4 T cells. Thus, mucosal DC subsets that are active producers of at-RA inhibit induction of Il10 in naive CD4 T cells while promoting induction of Foxp3. Accordingly, mice with vitamin A deficiency have increased numbers of IL-10\u2013competent T reg cells. Activation of DCs by certain Toll-like receptors (TLRs), particularly TLR9, suppresses T cell induction of Foxp3 and enables induction of Il10. Collectively, our data indicate that at-RA has reciprocal effects on the induction of Foxp3 and Il10 in developing CD4+ T reg cells and suggest that TLR9-dependent inhibition of at-RA production by antigen-presenting cells might represent one mechanism to promote the development of IL-10\u2013expressing T cells.<\/jats:p>","DOI":"10.1084\/jem.20080950","type":"journal-article","created":{"date-parts":[[2009,2,16]],"date-time":"2009-02-16T23:47:46Z","timestamp":1234828066000},"page":"343-357","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Contrasting roles for all-trans retinoic acid in TGF-\u03b2\u2013mediated induction of <i>Foxp3<\/i> and <i>Il10<\/i> genes in developing regulatory T cells"],"prefix":"10.1084","volume":"206","author":[{"given":"Craig L.","family":"Maynard","sequence":"first","affiliation":[{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin D.","family":"Hatton","sequence":"additional","affiliation":[{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney S.","family":"Helms","sequence":"additional","affiliation":[{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Stephensen","sequence":"additional","affiliation":[{"name":"Nutrition Department, United States Department of Agriculture Western Human Nutrition Research Center, University of California, Davis, Davis, CA 95616 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey T.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"},{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"},{"name":"Department of Pathology 1 , 2 , and 3"},{"name":"Department of Microbiology 1 , 2 , and 3"},{"name":"Department of Medicine, University of Alabama at Birmingham, AL 35294 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,2,9]]},"reference":[{"key":"2023072916421889700_bib1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nri821","article-title":"CD4+ CD25+ suppressor T cells: more questions than answers","volume":"2","author":"Shevach","year":"2002","journal-title":"Nat. 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