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Is there a role for IL-17 in the pathogenesis of systemic sclerosis?

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Published in Immunology Letters. 2017
Abstract In systemic sclerosis (SSc) immuno-inflammatory events are central to disease development. Amongst other mediators of inflammation, interleukin 17 (IL-17) and Th17 cells have been reported to be increased in the peripheral blood and target organs including involved skin in SSc. They participate and amplify inflammatory responses by inducing the production of cytokines such as IL-6, chemokines such as CCL2 and CXCL8 (IL-8), matrix metalloproteinases-1, -2, -9 and the expression of adhesion molecules in stromal cells including fibroblasts and endothelial cells. In this respect, IL-17 and Th17 cells behave paradigmatically as documented in other autoimmune pathological conditions or infectious diseases. In experimental animal models of skin and lung fibrosis, IL-17 indirectly enhances the fibrotic process by favoring further inflammation by recruiting inflammatory cells, by activating and/or stimulating the production of TGF-β and other pro-fibrotic mediators, by inhibiting autophagy. Whether the findings generated in animal models of fibrosis can be translated to human SSc is unproven. Furthermore, it is controversial whether IL-17 directly promotes the transdifferentiation of human fibroblasts into myofibroblasts and enhances collagen production, with most of the available evidence against this possibility. The reductionist approach in which fibroblast in monolayers are cultured in plastic dishes under the influence of IL-17 limits the relevance of these findings. Further in vitro/ex vivo models with human tissues are being developed to investigate the real effect of IL-17 on extracellular matrix deposition, since agents blocking IL-17 are available for the clinic and it will be important to know whether their use in SSc would be beneficial or detrimental.
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PMID: 28919455
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Research group La matrice extracellulaire (651)
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CHIZZOLINI, Carlo, DUFOUR, Aleksandra Maria, BREMBILLA, Nicolo. Is there a role for IL-17 in the pathogenesis of systemic sclerosis?. In: Immunology Letters, 2017. https://archive-ouverte.unige.ch/unige:99722

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Deposited on : 2017-11-28

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