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 <5% of kidney DCs, is poorly understood. We studied the role of CD103 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), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103 DCs and T 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 numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103 DCs and T 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, 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 and produced the chemokine CCL20, which is known to attract T into the kidney. Our findings show that CD103 DCs foster intrarenal FoxP3 T accumulation, thereby antagonizing proinflammatory CD11b DCs. Thus, increasing CD103 DC numbers or functionality might be advantageous in cGN.