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Career situation of first and presenting author Student for a master or a PhD. Introduction The synovial fluid of Juvenile idiopathic Arthritis (JIA) is rich of Th17 and of Th-17-derived CD4+ CD161+ cells, also called non-classic-Th1. How such subpopulations drive the JIA joint damage is still a subject of great interest especially in light of the possible use of biological drugs able to selectively inhibit the activity of specific cytokines. Objectives To clarify the role of Th17 and non-classical Th1 lymphocytes in the pathogenesis of joint cartilage destruction by synovial fibroblasts (SFbs). Methods The role of different subsets of CD4+T cells was observed in the activation of SFbs in terms of cartilage degradation by normal and JIA SFbs and induction of proteases both in vitro and in vivo, using a SCID Mouse model through the ‘inverse wrap’ implantation technique. Results JIA SFbs produce large amounts of MMP9 and efficiently degrade fragments of human cartilage wrapped in a collagen matrix containing the fibroblasts themselves and grafted under-skin on SCID mice (the ‘inverse wrap model’). Similar effects were observed with SFbs of healthy subjects incubated with conditioned media of Th17 and of non-classic Th1. We shown that Th17 induce MMP9 in SFbs, while non-classic Th1 act mainly by inducing urokinase-plasminogen-activator over-activity. Conclusions IL-17 triggers the pathogenic chain leading to joint damage in patients with JIA. References Maggi L, et al. T cell subpopulations in juvenile idiopathis arthritis and their modifications after biotherapies. Autoimmun Rev 2016;15:1141–44. Nistala K, et al. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A 2010;107:14751–6. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009 August 27;361:888–98. Maggi L, et al. Judex M, et al. ‘Inverse wrap’: an improved implantation technique for virus transduced synovial fibroblasts in the SCID mouse model forrheumatoid arthritis. Mod Rheumatol 2001;11:145–50. Del Rosso M, et al. Multiple pathways of cell invasion are regulated by multiple families of serine proteases. Clin Exp Metastasis 2002;19:193–207. Beringer A, Noack M, Miossec P. L-17 in Chronic Inflammation: From Discovery to Targeting. Trends Mol Med 2016 March;22:230–241. Miossec P. Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice. RMD Open 2017 February 15;3. Disclosure of Interest None declared. |
