Evers, Beatrix D. G. and Engel, Daniel R. and Boehner, Alexander M. C. and Tittel, Andre P. and Krause, Torsten A. and Heuser, Christoph and Garbi, Natalio and Kastenmueller, Wolfgang and Mack, Matthias and Tiegs, Gisa and Panzer, Ulf and Boor, Peter and Ludwig-Portugall, Isis and Kurts, Christian (2016) CD103(+) Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 27 (11). pp. 3368-3382. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)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 (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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FLT3 LIGAND; EXPERIMENTAL GLOMERULONEPHRITIS; RETINOIC-ACID; IN-VIVO; DE-NOVO; ANTIGEN; MICE; TOLERANCE; RECEPTOR; DISEASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2019 11:58 |
| Last Modified: | 05 Apr 2019 11:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4050 |
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