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We observed that impaired function of CD4+CD25+ regulatory T cells (Tregs) and increased cytokine levels of the IL-23\/Th17 pathway were responsible for the psoriatic phenotype in this mouse model. Treatment of K5.hTGF-\u03b21 transgenic mice with PUVA suppressed the IL-23\/Th17 pathway, Th1 milieu, as well as transcription factors STAT3 and orphan nuclear receptor ROR\u03b3t. PUVA induced the Th2 pathway and IL-10\u2013producing CD4+CD25+Foxp3+Tregs with disease-suppressive activity that was abolished by anti-CTLA4 mAb treatment. These findings were paralleled by macroscopic and microscopic clearance of the diseased murine skin. Anti\u2013IL-17 mAb treatment also diminished the psoriatic phenotype of the mice. This indicated that both induced Tregs involving CTLA4 signaling and inhibition of the IL-23\/Th17 axis are central for the therapeutic action of PUVA.<\/jats:p>","DOI":"10.4049\/jimmunol.0903719","type":"journal-article","created":{"date-parts":[[2010,5,19]],"date-time":"2010-05-19T23:07:04Z","timestamp":1274310424000},"page":"7257-7267","source":"Crossref","is-referenced-by-count":100,"title":["8-Methoxypsoralen Plus Ultraviolet A Therapy Acts via Inhibition of the IL-23\/Th17 Axis and Induction of Foxp3+ Regulatory T Cells Involving CTLA4 Signaling in a Psoriasis-Like Skin Disorder"],"prefix":"10.1093","volume":"184","author":[{"given":"Tej Pratap","family":"Singh","sequence":"first","affiliation":[{"name":"Research Unit for Photodermatology, Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center G\u00f6ttingen , G\u00f6ttingen"},{"name":"Department of Dermatology and Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Wallbrecht","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Rinner","sequence":"additional","affiliation":[{"name":"Center for Medical Research, Medical University of Graz , Graz,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerlinde","family":"Mayer","sequence":"additional","affiliation":[{"name":"Research Unit for Photodermatology, Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Schmidbauer","sequence":"additional","affiliation":[{"name":"Research Unit for Photodermatology, Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heimo","family":"Strohmaier","sequence":"additional","affiliation":[{"name":"Center for Medical Research, Medical University of Graz , Graz,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology"},{"name":"Department of Otolaryngology"},{"name":"Department of Dermatology"},{"name":"Department of Craniofacial Biology, Head and Neck Cancer Research, University of Colorado , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Wolf","sequence":"additional","affiliation":[{"name":"Research Unit for Photodermatology, Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,6,15]]},"reference":[{"key":"2026012806293813400_r1","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(00)04954-0","article-title":"Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial.","volume":"357","author":"Chaudhari","year":"2001","journal-title":"Lancet"},{"key":"2026012806293813400_r2","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1056\/NEJMoa030409","article-title":"Etanercept as monotherapy in patients with psoriasis.","volume":"349","author":"Leonardi","year":"2003","journal-title":"N. 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