{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:57:12Z","timestamp":1791291432342,"version":"4.3.0"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T00:00:00Z","timestamp":1351296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Although transforming growth factor \u03b2 (TGF\u03b2) and connective tissue growth factor (CTGF) have been considered to play central roles in the pathogenesis of systemic sclerosis (SSc), other cytokines may also be crucial for the development of SSc. The aim of this study was to examine the roles of T helper cytokines in the development of skin fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To compare the roles of Th1, Th2, and Th17 cytokines, we examined bleomycin\u2010induced SSc in mice deficient for interferon\u2010\u03b3 (IFN\u03b3), interleukin\u20104 (IL\u20104), and IL\u201017A. The mechanism by which IL\u201017A contributes to bleomycin\u2010induced fibrosis was investigated in vivo and in vitro. The outcome of mice lacking IL\u201017A was also investigated in TSK\u20101 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The loss of IL\u201017A significantly attenuated bleomycin\u2010induced skin fibrosis, whereas a deficiency of IFN\u03b3 or IL\u20104 did not. Leukocyte infiltration and the expression of TGF\u03b2 and CTGF messenger RNA in bleomycin\u2010injected skin were significantly reduced in IL\u201017A\u2013deficient mice compared with wild\u2010type (WT) mice. Daily bleomycin injections induced the expression of IL\u201017A in the skin and potent IL\u201017A producers in splenic CD4+ T cells from WT mice. Furthermore, a skin fibroblast cell line expressed increased TGF\u03b2, CTGF, and collagen after the addition of recombinant IL\u201017A. IL\u201017A deficiency also attenuated skin thickness in TSK\u20101 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that IL\u201017A contributes to skin fibrosis in 2 mouse models of SSc. These findings suggest that inhibition of IL\u201017A represents a therapeutic target for antagonizing fibrotic skin disorders such as SSc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34643","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T15:37:52Z","timestamp":1343230672000},"page":"3726-3735","source":"Crossref","is-referenced-by-count":135,"title":["Potential roles of interleukin\u201017A in the development of skin fibrosis in 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