These data suggest that miR-155 could inhibit Nrf2 leading to ROS overproduction and NLRP3 activation, this way contributing to SSc pathogenesis. 3.?ROS Photochlor and autoimmunity in SSc 3.1. an annual incidence ranging from 10.9 Photochlor cases/million up to 43 cases/million) . This chronic inflammatory disease is definitely characterized by vascular abnormalities, autoimmunity and fibrosis of the skin and visceral organs. Microangiopathy happens at an early step of the SSc as almost all individuals develop Raynaud trend and many display additional manifestations of small vessel disease, including ischemic digital ulcers, pulmonary arterial hypertension and renal arterial involvement associated with malignant hypertension and renal failure. Autoimmunity is definitely characterized by the presence in almost all individuals of autoantibodies directed against nuclear antigens with some specificity becoming associated with extension of pores and skin fibrosis and particular type of visceral involvement. Other autoantibodies directed against membrane antigens from fibroblasts and endothelial cells will also be frequently observed. Scleroderma is definitely characterized by an excessive production of extracellular matrix proteins (e. g. collagen) causing progressive interstitial and perivascular fibrosis of pores and skin and visceral organs (primarily lung, kidney and digestive tract). The extension of pores and skin fibrosis characterizes the form of the disease as diffuse or limited. The pathophysiology of SSc is very complex, with an connection of genetic and environmental factors. The disease needs a result in, such as an infection or exposure to harmful and happens on a vulnerable genetic background. Furthermore, several types of cells interact during SSc development such as innate and adaptive immune cells, fibroblasts, endothelial and clean muscle cells and are dysregulated in scleroderma. Despite an estimated heritability quite low (about 5%) in a study including 42 units of twins , having an affected first-degree relative increased the risk of SSc 13 instances compared to the general human population , therefore indicating that genetic factors play an important part in SSc. As in additional complex diseases, several genetic susceptibility loci have been identified, and for each, CD86 the relative odd percentage was quite low. However, most identified connected genes are concentrated in a few specific pathways involved in immunity, such as the HLA system, T-cell and B-cell co-stimulatory molecules, the type I interferon, the Interleukin-12 and the TNF pathway and family as well as molecules involved in the debris clearance, autophagy and various detoxification mechanisms, . Exposure to harmful or infectious providers remains the major environmental factors that result in the disease. Their pathophysiological effects seem to involve the induction of an oxidative burst that 1st effects endothelial cells leading to vascular hyperreactivity, endothelial cells apoptosis and ischemia reperfusion events which may participate in a vicious circle of ROS overproduction causing autoimmunity by ROS-induced antigen post-translational modifications. Overproduction of ROS and activation of endothelial and immune cells lead to chronic swelling and activate fibroblasts causing aberrant wound healing and fibrosis of the skin and visceral organs. Data from animal model support this sequence of events. Indeed, a chronic oxidative stress of the skin induced by direct exposure to pro-oxidative agents such as hydroxyl radicals, hypochlorous acid or bleomycin is sufficient to induce all the feature of the disease with fibrosis of the skin and visceral organs, vascular involvement and autoimmunity . 1.2. ROS in SSc In individuals with SSc, an oxidative stress, as defined by an imbalance between an oxidant and an anti-oxidant claims, is classically observed. Indeed, relating to a recent meta-analysis, several oxidative stress biomarkers, such as malondialdehyde (MDA- a marker of lipid peroxydation), nitric oxide and endogenous nitric oxide inhibitor asymmetric dimethylarginine (ADMA) are found higher in the blood of SSc individuals than in settings . By contrast, anti-oxidative biomarkers, such as superoxide dismutase and vitamin C, are reduced SSc individuals blood Photochlor than in settings . Oxidative-induced post-translational protein modifications, such as advanced oxidation protein products (AOPP) will also be improved in the plasma of SSc individuals compared to non-SSc settings . In SSc, the oxidative stress biomarkers were also found elevated in additional biological samples apart from blood. SSc individuals possess higher urinary levels of 8-Oxo-2-deoxyguanosine (8-oxodG) and isoprostanes that are produced by free radical-catalyzed peroxidation of arachidonic acid compared to settings . In addition and relevant to the visceral involvement of the disease especially in the lung, individuals with systemic sclerosis.