CD22 and CD72 contribute to the development of scleroderma in a murine model

Abstract Background Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by excessive fibrosis. CD22 and CD72 are B cell-specific cell surface molecules that negatively regulate B cell function. Objective The aim of the present study was to investigate the roles of CD22 and CD72 in a murine scleroderma model. Methods The experimental fibrosis model was generated by subcutaneous injection of bleomycin or hypochlorous acid (HOCL) into wild-type (WT), CD22-deficient (CD22−/−), CD72-deficient (CD72−/−) and CD22 and CD72 double-deficient (CD22−/−/CD72−/−) mice. We histologically assessed skin fibrosis and inflammatory cell infiltration. Cytokine and chemokine expression levels were measured by real-time polymerase chain reaction. Results The severity of fibrosis in the skin and lung was significantly less in CD22−/−, CD72−/−, and CD22−/−/CD72−/− mice than in WT mice in the bleomycin-induced model. In the skin of bleomycin-treated mice, the numbers of CD3+ T cells, CD8+ T cells, and F4/80+ macrophages were significantly lower in CD22−/−, CD72−/−, and CD22−/−/CD72−/− mice than in WT mice. The expression levels of mRNAs for IL-6, TNF-α, TGF-β, CTGF, IL-1β, IL-13, CXCL2, and ICAM-1 were significantly lower in CD22−/−, CD72−/−, and CD22−/−/CD72−/− mice than in WT mice. In the HOCL-induced model, both skin and lung fibrosis were ameliorated in CD22−/−, CD72−/− and CD22−/−/CD72−/− mice compared to WT mice. Conclusion These results indicate that CD22 and CD72 likely play crucial roles in skin and lung fibrosis. Moreover, the inhibition of CD22 and CD72 function has potential as a therapeutic approach to SSc.