FRI0522 Peripheral Blood Mononuclear Cells Co-Cultured with Autologous Skin Fibroblasts Up-Regulate IL-17A and Play Anti-Fibrotic Effects in Systemic Sclerosis

Background IL-17A has been recently implicated in the pathogenesis of systemic sclerosis (SSc). Objectives Therefore, we explored its expression and effects in peripheral blood mononuclear cells (PBMCs) co-cultured with autologous skin fibroblasts. Methods PBMCs and autologous skin fibroblasts from 5 patients with early (disease duration Results Real-time PCR analysis showed an increased expression of IL17A in co-cultured PBMCs by 11.5 fold (p Lastly, we investigated the effects of co-cultured PBMCs on the expression of pro-fibrotic genes in fibroblasts. We found that COL1A1, COL3A1, and CTGF mRNAs were down-regulated by 0.33 fold, 0.24 fold, and 0.31 fold respectively (p Conclusions Here we show for the first time that PBMCs from early dcSSc co-cultured with autologous skin fibroblasts over-express IL17A and exert anti-fibrotic effects in vitro. The simultaneous up-regulation of IL17RA and IL-17A target genes in the co-cultured fibroblasts suggests that IL-17A pathway is active in early dcSSc fibroblasts. These findings are paralleled by the down-regulation of TGF-beta signalling components. We previously showed that in co-cultures performed with PBMCs and autologous skin fibroblasts from early dcSSc patients T cells are expanded and kill the autologous fibroblasts. Taken together, these novel data support the hypothesis that immune system may be primarily aimed to control fibroblast activation in the early phases of the disease, potentially opening new therapeutic approaches in SSc. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5910