{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:51:41Z","timestamp":1790801501379,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T00:00:00Z","timestamp":1415577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Interleukin\u201019 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019) plays an important role in asthma by stimulating T helper type 2 (Th2) cytokine production. Interestingly, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, a key Th2 cytokine, in turn up\u2010regulates <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 expression in bronchial epithelial cells, so forming a positive feedback loop. In atopic dermatitis (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>), another Th2 disease closely related to asthma, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 is up\u2010regulated in the skin. We propose to use <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 transgenic (Tg) mice and human keratinocyte culture to delineate the molecular mechanisms involved in the up\u2010regulation of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 is similarly up\u2010regulated in the skin of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 Tg mice as in human <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. Next we show that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 up\u2010regulates <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 expression in keratinocytes. Interestingly, the up\u2010regulation was suppressed by a pan\u2010Janus kinase (Jak) inhibitor, suggesting that the Jak\u2013signal transducer and activator of transcription (Jak\u2010STAT) pathway may be involved. Dominant negative studies further indicate that STAT6, but not other STATs, mediates the up\u2010regulation. Serial 5\u2032 deletion of the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 promoter and mutagenesis studies demonstrate that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 up\u2010regulation of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 in keratinocytes involves two imperfect STAT6 response elements. Finally, chromatin immunoprecipitation assay studies indicate that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 increases the binding of STAT6 to its response elements in the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 promoter. Taken together, we delineate the detailed molecular pathway for <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 up\u2010regulation of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201019 in keratinocytes, which may play an important role in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> pathogenesis.<\/jats:p>","DOI":"10.1111\/imm.12339","type":"journal-article","created":{"date-parts":[[2014,6,18]],"date-time":"2014-06-18T23:32:15Z","timestamp":1403134335000},"page":"601-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Interleukin\u20104 up\u2010regulation of epidermal interleukin\u201019 expression in keratinocytes involves the binding of signal transducer and activator of transcription 6 (Stat6) to the imperfect Stat6 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