Expression Level And Methylation Status Of CD70in CD4+T Cells From Patients With Systemic Sclerosis

Objective:So far the pathogenesis of scleroderma or systemic sclerosis (SSc) is still unclear. CD70, a B cell costimulatory molecule that interacts with CD27during B-T cell contact to promote plasma cell differentiation and immunoglobulin production and to increase the cytotoxic capacity of activated natural killer cells, is overexpressed due to hypomethylation of its promoter regulatory elements in CD4+T cells from patients with the following autoimmune diseases, namely systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and primary Sjo" gren’s syndrome (pSS). However, as an autoimmune disease, it is unknown whether aberrant expression and methylation of CD70occur in CD4+T cells from patients with SSc. There is no relevant information at home and abroad. In this study, we investigate the expression levels and methylation patterns of CD70in CD4+T cells from SSc patients and healthy controls, aiming to discover the aberrant epigenetic regulations in SSc and open up new avenues for revealing the pathogenesis of SSc.Methods:Flow cytometry and real time PCR were used to compare the expessions of CD70and the mRNA levels of CD70in CD4+T cells from patients with SSc and healthy controls, respectively. Bisulfite sequencing was used to determine the methylation status of the TNFSF7(CD70) promoter region.Result:CD70mRNA and protein levels are significantly increased(P=0.001, P=0.006; respectively) in CD4+T cells of SSc patients compared to controls. The TNFSF7promoter is demethylated in CD4+T cells of SSc patients (P=0.019) compared to controls. There was a significantly negative correlation between the expression of CD70and TNFSF7promoter methylation level in SSc CD4+T cells(r=-0.616, P=0.004).Conclusion:The demethylation of CD70promoter region contributes to the overexpression of CD70in CD4+T cells and may contribute to autoimmune response in SSc.