B7-H3 immune modulatory molecule has been implicated in the generation and pathogenesis of autoimmune diseases, the mechanism of action is less known. We explored the role of B7-H3 in the induction of autoantibodies and organ-directed inflammation in a murine systemic lupus erythematosus (SLE) model in which the immunization with DNA extracted from activated T cells induced the production of anti-DNA autoantibodies and subsequent glomerulonephritis, two hallmarks of human SLE. Mice deficient of B7-H3 or treated with a B7-H3 specific antibody produced significantly higher levels of anti-DNA autoantibodies and more severe glomerulonephritis than wild-type mice, indicating an inhibitory function of B7-H3 in this model. Interestingly, immunization of mice with DNA-pulsed dendritic cells induced severe SLE symptoms while B7-H3 on dendritic cells is required in this process. Importantly, treatment of mice with recombinant B7-H3Ig fusion protein effectively ameliorated progression of murine SLE, accompanied with decreased level of anti-DNA autoantibodies and alleviated glomerulonephritis, decreased autoantibody deposition and complement deposition in kidney. Our findings implicate a potential role of B7-H3 on dendritic cells in the induction of SLE and as a potential target for the treatment of autoimmune diseases.
Animals Antibodies