LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE

IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an inflammatory infiltrate is characteristic of the early phases of fibrosis development and inflammatory cells may profoundly affect the ECM production by releasing soluble products or by direct cell-to-cell interactions that modify fibroblast metabolism. Fibrosis is characteristic of many diseases, as systemic sclerosis (SSc), morphea, acrodermatitis chronica atrophicans, Shulman fasciitis and the cutaneous form of graft versus host disease (GVHD). In particular has been shown that IL-17A is present not only in the biological fluids but also in the skin of individuals affected by SSc. The aims of this study are to understand if the IL-17 isoforms are expressed in the skin of individuals affected by these diseases and which are the cells responsible for the production of IL-17A. Moreover we are interested in understanding if the treatment with Iloprost or NAC can modify the expression of the IL-17 isoforms in the skin of SSc patients and if also the cells responsible for the production of IL-17A are modified by these drugs. Bioptic material was obtained from the involved individuals affected by different fibrotic diseases and from healthy donors (HD) undergoing plastic surgery. We adopted an immunohistochemistry and immunofluorescence approach to identify and quantify in vivo the presence of cells positive for the IL-17 isoforms, the IL-17 receptors, IL-4, IL-22, INF-γ, CD3 and Tryptase. All the IL-17 isoforms are expressed in all the bioptic samples analyzed, without significant differences between the HD and the pathologic groups. IL-17A is produced by both CD3 and mast cells, and are significantly more numerous in the HD than in the SSc skin (p=0,0485). The expression of the IL-17 isoforms in the skin of SSc patients treated with Iloprost changes unevenly in all the patients. The same happens for the expression of IL-17C in the skin of SSc individuals treated with NAC, while these patients show a marked (but not significant) increase number of IL-17A and IL-17F positive cells and a decreased number of IL-17E positive cells. The treatment with Iloprost induces also the decrease in the number of both CD3 and mast cells producing IL-17A, while NAC induces the increase in the number of CD3 IL-17A producing cells. The number of mast cells producing IL-17A in patients treated with NAC changes unevenly. The number of CD3 and mast cells that produce IL-17A does not reflect the total number of IL-17A positive cells localized in the analyzed samples. This could mean that other cell types are responsible for IL-17A production. Given the role of the IL-17 isoforms in the immunity and inflammatory pathway, the presence of these cytokines in the skin of patients affected by fibrotic diseases can mean that they can be involved in the fibrotic process. This is confirmed by the modification of the expression of the IL-17 isoforms in the skin of patients treated with Iloprost or NAC. In particular it seems that IL-17A and IL-17F can have a pro-fibrotic role, while IL-17E can have an anti-fibrotic role in the SSc pathogenesis.