| First Author | Evers BD | Year | 2016 |
| Journal | J Am Soc Nephrol | Volume | 27 |
| Issue | 11 | Pages | 3368-3382 |
| PubMed ID | 27036736 | Mgi Jnum | J:293111 |
| Mgi Id | MGI:6437024 | Doi | 10.1681/ASN.2015080873 |
| Citation | Evers BD, et al. (2016) CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells. J Am Soc Nephrol 27(11):3368-3382 |
| abstractText | 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. |
