Dataset Information


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

ABSTRACT: 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 (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs 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 Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs 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 Tregs, 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 Tregs and produced the chemokine CCL20, which is known to attract Tregs 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.


PROVIDER: S-EPMC5084885 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3196467 | BioStudies
2014-01-01 | S-EPMC3994898 | BioStudies
2010-01-01 | S-EPMC2856032 | BioStudies
2014-01-01 | S-EPMC3925240 | BioStudies
2014-01-01 | S-EPMC4144807 | BioStudies
2020-01-01 | S-EPMC7522802 | BioStudies
1000-01-01 | S-EPMC5436540 | BioStudies
2018-01-01 | S-EPMC5964519 | BioStudies
2016-01-01 | S-EPMC4801902 | BioStudies
1000-01-01 | S-EPMC2442640 | BioStudies