Zusammenfassung
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 ...
Zusammenfassung
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-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 Treg 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(+) Treg accumulation, thereby antagonizing proinflammatory CD11b(+) DCs. Thus, increasing CD103(+) DC numbers or functionality might be advantageous in cGN.
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