{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:14:03Z","timestamp":1776179643257,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances such responses. To identify a potential mechanism(s) underlying this in vivo activity of vitamin A, we examined the effects of all-trans and 9-cis RA on development of Th1 and Th2 cell populations using in vitro stimulation of Ag-naive Th0 cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, but not with all-trans RA, at primary stimulation strongly enhanced Th2 development. IL-4-neutralizing Ab blocked this activity, but IL-12- and IFN-\u03b3-neutralizing Ab did not. Because 9-cis RA regulates gene transcription via either RA receptors or retinoid X receptors (RXRs), we tested the Th2-enhancing activities of the RXR- and RA receptor-selective agonists AGN194204 and 4-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TTNPB). AGN194204 strongly enhanced Th2 development, whereas TTNPB did not. This RXR agonist also enhanced Th2 development when purified, naive Th0 cells (L-selectinhigh\/CD4+) were stimulated with CD3 and CD28 Abs in the absence of APCs. During primary antigenic stimulation of naive Th0 cells from DO11.10 mice, AGN194204 increased IL-4 and IL-5 production, decreased IFN-\u03b3 production, increased mRNA in responding T cells for genes involved in Th2 development (IL-4, GATA-3, and c-maf), and decreased mRNA for genes involved in Th1 development (IFN-\u03b3, T-bet, and IL-12R). These data show that stimulation of the RXR pathway enhances Th2 development, perhaps by affecting the relative expression of pertinent transcription factors, cytokines, and cytokine receptors.<\/jats:p>","DOI":"10.4049\/jimmunol.168.9.4495","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:46:54Z","timestamp":1398023214000},"page":"4495-4503","source":"Crossref","is-referenced-by-count":121,"title":["Vitamin A Enhances in Vitro Th2 Development Via Retinoid X Receptor Pathway"],"prefix":"10.1093","volume":"168","author":[{"given":"Charles B","family":"Stephensen","sequence":"first","affiliation":[{"name":"U.S. Department of Agriculture Western Human Nutrition Research Center and Nutrition Department, University of California , Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuven","family":"Rasooly","sequence":"additional","affiliation":[{"name":"U.S. Department of Agriculture Western Human Nutrition Research Center and Nutrition Department, University of California , Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Jiang","sequence":"additional","affiliation":[{"name":"U.S. Department of Agriculture Western Human Nutrition Research Center and Nutrition Department, University of California , Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Ceddia","sequence":"additional","affiliation":[{"name":"U.S. Department of Agriculture Western Human Nutrition Research Center and Nutrition Department, University of California , Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey T","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Alabama , Birmingham, AL 35243"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshantha A S","family":"Chandraratna","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biology, Retinoid Research , Allergan, Irvine, CA 92623"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R Patterson","family":"Bucy","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Alabama , Birmingham, AL 35243"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,5,1]]},"reference":[{"key":"2026020209025712300_R1","first-page":"366","volume-title":"BMJ","year":"1993"},{"key":"2026020209025712300_R2","first-page":"898","volume-title":"J. Am. Med. Assoc.","year":"1993"},{"key":"2026020209025712300_R3","first-page":"979","volume-title":"FASEB J.","year":"1996"},{"key":"2026020209025712300_R4","first-page":"5878","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1987"},{"key":"2026020209025712300_R5","first-page":"441","volume-title":"J. Infect. Dis.","year":"1994"},{"key":"2026020209025712300_R6","first-page":"581","volume-title":"Immunology","year":"1993"},{"key":"2026020209025712300_R7","first-page":"94","volume-title":"J. Nutr.","year":"1996"},{"key":"2026020209025712300_R8","first-page":"388","volume-title":"J. Immunol.","year":"1989"},{"key":"2026020209025712300_R9","first-page":"1673","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020209025712300_R10","first-page":"1515","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020209025712300_R11","first-page":"546","volume-title":"Biochem. Biophys. Acta","year":"2001"},{"key":"2026020209025712300_R12","first-page":"1132","volume-title":"J. Nutr.","year":"2000"},{"key":"2026020209025712300_R13","first-page":"450","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020209025712300_R14","first-page":"1062","volume-title":"J. Nutr.","year":"1992"},{"key":"2026020209025712300_R15","first-page":"26783","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020209025712300_R16","first-page":"1866","volume-title":"Science","year":"2001"},{"key":"2026020209025712300_R17","first-page":"319","volume-title":"The Retinoids: Biology, Chemistry and Medicine","year":"1994"},{"key":"2026020209025712300_R18","first-page":"257","volume-title":"Annu. Rev. Nutr.","year":"1996"},{"key":"2026020209025712300_R19","first-page":"2140","volume-title":"Science","year":"2000"},{"key":"2026020209025712300_R20","first-page":"3372","volume-title":"Mol. Cell. Biol.","year":"1999"},{"key":"2026020209025712300_R21","first-page":"2298","volume-title":"J. Med. Chem.","year":"2001"},{"key":"2026020209025712300_R22","first-page":"1720","volume-title":"Science","year":"1990"},{"key":"2026020209025712300_R23","first-page":"1635","volume-title":"J. Exp. Med.","year":"1983"},{"key":"2026020209025712300_R24","first-page":"G589","volume-title":"Am. J. Physiol.","year":"1997"},{"key":"2026020209025712300_R25","first-page":"649","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020209025712300_R26","first-page":"1247","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020209025712300_R27","first-page":"2289","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209025712300_R28","first-page":"643","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020209025712300_R29","first-page":"134","volume-title":"Clin. Immunol.","year":"1999"},{"key":"2026020209025712300_R30","first-page":"3817","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020209025712300_R31","first-page":"973","volume-title":"Cell","year":"1996"},{"key":"2026020209025712300_R32","first-page":"1859","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209025712300_R33","first-page":"313","volume-title":"Immunity","year":"1996"},{"key":"2026020209025712300_R34","first-page":"479","volume-title":"Immunol. Today","year":"2000"},{"key":"2026020209025712300_R35","first-page":"655","volume-title":"Cell","year":"2000"},{"key":"2026020209025712300_R36","first-page":"1677","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1996"},{"key":"2026020209025712300_R37","first-page":"1962","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020209025712300_R38","first-page":"6065","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1992"},{"key":"2026020209025712300_R39","first-page":"75","volume-title":"Cell. Immunol.","year":"1998"},{"key":"2026020209025712300_R40","first-page":"4974","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020209025712300_R41","first-page":"1098","volume-title":"Eur. J. Immunol.","year":"2001"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/168\/9\/4495\/62551046\/4495.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/168\/9\/4495\/62551046\/4495.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:03:34Z","timestamp":1770041014000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/168\/9\/4495\/8024930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,1]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2002,5,1]]},"published-print":{"date-parts":[[2002,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.168.9.4495","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2002,5]]},"published":{"date-parts":[[2002,5,1]]}}}