CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T Cells

Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b + subset and promote crescentic GN (cGN). The function of the CD103 + subset, which represents + DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3 + intrarenal regulatory T cells (T regs ), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103 + DCs and T regs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103 + DC numbers by 50% in Langerin-DTR mice halved T reg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103 + DCs and T regs than Langerin-DTR mice but exhibited milder cGN than did Batf3 −/− mice presumably because proinflammatory CD11b + DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103 + DCs and T regs , but also of proinflammatory CD11b + DCs. On antibody-mediated removal of CD11b + DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103 + DCs caused cocultured T cells to differentiate into T regs and produced the chemokine CCL20, which is known to attract T regs into the kidney. Our findings show that CD103 + DCs foster intrarenal FoxP3 + T reg accumulation, thereby antagonizing proinflammatory CD11b + DCs. Thus, increasing CD103 + DC numbers or functionality might be advantageous in cGN.