{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:12:23Z","timestamp":1791227543936,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T00:00:00Z","timestamp":1367971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:p>The aryl hydrocarbon receptor (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>) is a key transcriptional regulator of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h17\u2010cell differentiation. Although endogenous ligands have yet to be identified, evidence suggests that tryptophan metabolites can act as agonists for the <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>. Tryptophan metabolites are abundant in circulation, so we hypothesized that cell intrinsic factors might exist to regulate the exposure of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h17 cells to <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010dependent activities. Here, we find that <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h17 cells preferentially express kynurenine 3\u2010monooxygenase (<jats:styled-content style=\"fixed-case\">KMO<\/jats:styled-content>), which is an enzyme involved in catabolism of the tryptophan metabolite kynurenine. <jats:styled-content style=\"fixed-case\">KMO<\/jats:styled-content> inhibition, either with a specific inhibitor or via si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated silencing, markedly increased <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 production in vitro, whereas <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 production by <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h1 cells was unaffected. Inhibition of <jats:styled-content style=\"fixed-case\">KMO<\/jats:styled-content> significantly exacerbated disease in a <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h17\u2010driven model of autoimmune gastritis, suggesting that expression of <jats:styled-content style=\"fixed-case\">KMO<\/jats:styled-content> by <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h17 cells serves to limit their continuous exposure to physiological levels of endogenous <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> ligands in vivo.<\/jats:p>","DOI":"10.1002\/eji.201242779","type":"journal-article","created":{"date-parts":[[2013,4,9]],"date-time":"2013-04-09T08:12:57Z","timestamp":1365495177000},"page":"1727-1734","source":"Crossref","is-referenced-by-count":41,"title":["Kynurenine 3\u2010monooxygenase mediates inhibition of <scp>T<\/scp>h17 differentiation via catabolism of endogenous aryl hydrocarbon receptor ligands"],"prefix":"10.1002","volume":"43","author":[{"given":"Geoffrey L.","family":"Stephens","sequence":"first","affiliation":[{"name":"Respiratory, Inflammatory, and Autoimmune Diseases Research  MedImmune, LLC Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Wang","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammatory, and Autoimmune Diseases Research  MedImmune, LLC Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Swerdlow","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammatory, and Autoimmune Diseases Research  MedImmune, LLC Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Bhat","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammatory, and Autoimmune Diseases Research  MedImmune, LLC Gaithersburg MD 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