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

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-ß, CTGF, IL-1ß, 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.