Background. IL-23, pro-inflammatory cytokine belonging to the IL-12 family, is essential for the differentiation of Th17 lymphocytes, which induces cytokines including IL-17, IL-17F, IL-22, IL-6 and TNF-α. Although IL-23 may play a key role in autoimmune diseases and inflammatory diseases, its role in the regulatory mechanism of extracellular matrix and its contribution to the phenotype of systemic sclerosis (SSc) is still unknown.Objectives. To investigate the role of IL-23 in the pathogenesis of SSc.Methods. The expression profile of extracellular matrix-related genes was assessed by gene array. The protein expression of type I collagen and IL-23 receptor was determined by immunoblotting. Results. PCR array showed IL-23 had no significant effect on extracellular matrix-related gene expression including collagens in cultured human dermal fibroblasts. However, protein levels of type I collagen in normal fibroblasts were decreased by the treatment with IL-23, suggesting that IL-23 induces collagen expression post-transcriptionally. IL-12 did not affect the type I collagen protein expression. The expression of IL-23 receptor in SSc fibroblasts was significantly decreased compared with that in normal fibroblasts, due to the intrinsic TGF-β activation in these cell types. Conclusion. Our results suggest that IL-23 signaling has an anti-fibrotic effect via the down-regulation of collagen expression. IL-23 signaling is suppressed due to the down-regulation of the receptor by the intrinsic activation of TGF-β1 in SSc fibroblasts, which may amplify the increased collagen accumulation and fibrosis characteristic of SSc. Clarifying the novel regulatory mechanisms of fibrosis by the cytokine network consisted of TGF-β and IL-23 may lead to new therapeutic approach. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF