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Dendritic cell‐targeted CD40 DNA vaccine suppresses Th17 and ameliorates progression of experimental autoimmune glomerulonephritis

The CD40‐CD40L costimulatory pathway is critical for T cell activation in autoimmune disease. We have previously found that blocking the CD40‐CD40L pathway using a dendritic cell‐targeted CD40 DNA (DEC‐CD40) vaccine prevented the development of Heymann nephritis. In this study, we explored the effect of a DEC‐CD40 vaccine in the treatment of experimental autoimmune glomerulonephritis (EAG), an animal model of human Goodpasture's disease induced by antigen α3IV‐NC1. DEC‐CD40 vaccine given at week 3 and week 6 after 3IV‐NC1 injection reduced kidney structural and functional injury significantly in EAG. DEC‐CD40 vaccination suppressed Th17 cell numbers and Th17 immune responses in kidney and spleen, but did not alter Th1 cells number and responses. Serum derived from rats with DEC‐CD40 vaccination suppressed Th17 differentiation, but not Th1 differentiation in vitro. Furthermore, B cell activation, driven by Th17 cytokines, was suppressed by serum from rats vaccinated with DEC‐CD40. A DNA vaccine encoding CD40 and targeting dendritic cell, ameliorates kidney injury in both early and late stages in EAG rats, indicating DEC‐CD40 vaccination has a therapeutic role in EAG. Its effect is associated with the reduction of Th17 differentiation and Th17‐mediated B cell activation.