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By crossing R26Stat3C<jats:sup>stopfl\/fl<\/jats:sup> CD4Cre mice onto an interleukin\u201022 (IL\u201022)\u2013knockout background or treating the mice with a neutralizing antibody against IL\u201017, we interrogated how these Th17 cytokines could contribute to the pathogenesis of PsA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>R26Stat3C<jats:sup>stopfl\/fl<\/jats:sup> CD4Cre mice developed acanthosis, hyperkeratosis, and parakeratosis of the skin, as well as enthesitis\/tendinitis and periarticular bone erosion in different joints, accompanied by osteopenia. T cell\u2013specific expression of a hyperactive Stat3C allele was found to drive the augmented Th17 response in these animals. Careful characterization of the mouse bone marrow revealed an increase in osteoclast progenitor (OCP) and RANKL\u2010producing cells, which contributed to the osteopenia phenotype observed in the mutant animals. Abrogation of the Th17 cytokines IL\u201017 or IL\u201022 improved both the skin and bone phenotype in R26Stat3C<jats:sup>stopfl\/fl<\/jats:sup> CD4Cre mice, revealing a central role of Th17 cells in the regulation of OCP and RANKL expression on stromal cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Perturbation of the IL\u201023\/Th17 axis instigates Th17\u2010mediated inflammation in R26Stat3C<jats:sup>stopfl\/fl<\/jats:sup> CD4Cre mice, leading to cutaneous and synovio\u2010entheseal inflammation and bone pathologic features highly reminiscent of human PsA. Both IL\u201017A and IL\u201022 produced by Th17 cells appear to play critical roles in promoting the cutaneous and musculoskeletal inflammation that characterizes PsA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40447","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T17:11:12Z","timestamp":1518541872000},"page":"855-867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Augmented Th17 Differentiation Leads to Cutaneous and Synovio\u2010Entheseal Inflammation in a Novel Model of Psoriatic Arthritis"],"prefix":"10.1002","volume":"70","author":[{"given":"Lu","family":"Yang","sequence":"first","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania H.","family":"Fanok","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New 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