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Renal Dendritic Cells Stimulate IL-10 Production and Attenuate Nephrotoxic Nephritis

Juliane Scholz^*, Veronika Lukacs-Kornek^*, Daniel R. Engel^*, Sabine Specht, Eva Kiss, Frank Eitner, Jürgen Floege, Herrmann-Josef Groene and Christian Kurts^*

^* Institute for Molecular Medicine and Experimental Immunology and Institute for Medical Microbiology, Immunologie and Parasitology, University of Bonn, Bonn, Germany; Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Heidelberg, Germany; and Division of Nephrology and Clinical Immunology, RWTH University of Aachen, Aachen, Germany

Correspondence: Dr. Christian Kurts, Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, 53105 Bonn, Germany. Phone: +49-228-287-11031; Fax: +49-228-287-11052; E-mail: ckurts{at}web.de

Received for publication June 19, 2007. Accepted for publication September 28, 2007.

The role of renal dendritic cells (DCs) in glomerulonephritis is unknown. This question was addressed in nephrotoxic nephritis, a murine model of human necrotizing glomerulonephritis, which is dependent on CD4⁺ Th1 cells and macrophages. DCs in nephritic kidneys showed signs of activation, accumulated in the tubulo-interstitium, and infiltrated the periglomerular space surrounding inflamed glomeruli. In ex vivo coculture experiments with antigen-specific CD4⁺ T cells, DCs stimulated the secretion of IL-10, which is known to attenuate nephrotoxic nephritis, and the Th1 cytokine IFN. Endogenous renal CD4⁺ T cells produced both of these cytokines as well, but those from nephritic mice secreted increased amounts of IL-10. Renal DCs were found to express ICOS-L, an inducer of IL-10. To evaluate the in vivo role of renal DCs in disease, CD11c⁺ DCs were depleted on days 4 and 10 after the induction of nephritis by injecting CD11c-DTR/GFP mice with diphtheria toxin. Sparing DCs until day 4 did not affect the autologous phase of nephritis. The number of renal DCs was reduced by 70% to 80%, the number of renal macrophages was unchanged, and periglomerular infiltrates were eliminated. On days 11 to 14, we observed aggravated tubulointerstitial and glomerular damage, reduced creatinine clearance, and increased proteinuria. These findings demonstrate that renal DCs exert a renoprotective effect in nephrotoxic nephritis, possibly by expressing ICOS-L and/or by inducing IL-10 in infiltrating CD4⁺ Th1 cells.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673