title: 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 Tregsthan 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 Tregnumbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+DCs and Tregsthan 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 Tregsand produced the chemokine CCL20, which is known to attract Tregsinto the kidney. Our findings show that CD103+DCs foster intrarenal FoxP3+Tregaccumulation, thereby antagonizing proinflammatory CD11b+DCs. Thus, increasing CD103+DC numbers or functionality might be advantageous in cGN.
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Beatrix D G
authors.initials: BD
authors.lastname: Evers
authors.affiliation: 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.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Engel
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Alexander M C
authors.initials: AM
authors.lastname: Böhner
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: André P
authors.initials: AP
authors.lastname: Tittel
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Torsten A
authors.initials: TA
authors.lastname: Krause
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heuser
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
authors.affiliation: Department of Internal Medicine II and Center for Interventional Immunology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Institute of Experimental Immunology and Hepatology and.
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.affiliation: III Clinic of Nephrology, University Clinic Eppendorf, Hamburg, Germany; and.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: Institute of Pathology and Department of Nephrology, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany.
authors.forename: Isis
authors.initials: I
authors.lastname: Ludwig-Portugall
authors.affiliation: Institute of Experimental Immunology, University Clinic of the Rheinische Friedrich Wilhelms Universität, Bonn, Germany; ckurts@web.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D007668:Kidney / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins; D016753:Interleukin-10
keywords: dendritic cells; glomerulonephritis; immunology; lymphocytes; regulatory T cells