CD22 and CD72 cooperatively contribute to the development of the reverse Arthus reaction model

Abstract Background Local type III hypersensitivity reactions are acute inflammatory events induced by immune complex (IC) deposition. CD22 and CD72 are B cell-specific cell surface molecules that negatively regulate B cell function. Objective To elucidate the roles of CD22 and CD72 in the development of IgG-mediated type III hypersensitivity reactions. Method The reverse Arthus reaction model in the skin was induced in mice lacking CD22 (CD22 -/- ), CD72 (CD72 -/- ), and both of them (CD22 -/- /CD72 -/- ). Edema at 4 hours and hemorrhage at 8 hours after IC challenge were evaluated. Inflammatory cell infiltration and cytokine and chemokine expression were also examined. Results Edema and hemorrhage were significantly reduced in CD22 -/- /CD72 -/- mice compared with wild-type mice. The loss of both membrane proteins resulted in a greater decrease in edema at 4 hours, but not hemorrhage at 8 hours, than the loss of each protein alone. Infiltration of neutrophils, macrophages, and T cells, and the expression of TNF-α, IL-6, MIP-1α, and CCR5 mRNA were also diminished in the knockout mice compared to wild-type mice, and most significantly reduced in CD22 -/- /CD72 -/- mice. Regulatory T (Treg) cells in the spleen were significantly increased in all knockout mice at 4 hours. Significant differences in the severity of edema and hemorrhage between wild-type and knockout mice were lost when Treg cells were depleted in the knockout mice. Conclusion These results demonstrate that CD22 and CD72 expression contribute to the development of the reverse Arthus reaction model and CD22 and CD72 might be therapeutic targets for human IC-mediated diseases.