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

Autor:	Evers BD; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Engel DR; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.; Institute for Experimental Immunology and Imaging, University Duisburg-Essen and University Hospital Essen, Essen, Germany., Böhner AM; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Tittel AP; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Krause TA; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Heuser C; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Garbi N; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Kastenmüller W; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Mack M; Department of Internal Medicine II and Center for Interventional Immunology, University Hospital Regensburg, Regensburg, Germany., Tiegs G; Institute of Experimental Immunology and Hepatology and., Panzer U; III Clinic of Nephrology, University Clinic Eppendorf, Hamburg, Germany; and., Boor P; Institute of Pathology and Department of Nephrology, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany., Ludwig-Portugall I; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany., Kurts C; Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany; ckurts@web.de.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2016 Nov; Vol. 27 (11), pp. 3368-3382. Date of Electronic Publication: 2016 Apr 01.
DOI:	10.1681/ASN.2015080873
Abstrakt:	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 T regs , 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 ⁺ T reg accumulation, thereby antagonizing proinflammatory CD11b ⁺ DCs. Thus, increasing CD103 ⁺ DC numbers or functionality might be advantageous in cGN. (Copyright © 2016 by the American Society of Nephrology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu