title: Kidney Dendritic Cells Become Pathogenic during Crescentic Glomerulonephritis with Proteinuria.
abstract: It is unclear why kidney dendritic cells attenuate some models of kidney disease but aggravate others. Kidney dendritic cells ameliorate the early phase of nonaccelerated nephrotoxic nephritis, a murine model of crescentic glomerulonephritis, but their effect on the later phase is unknown. Here, we report that kidney dendritic cells at later stages of nephrotoxic nephritis expressed higher levels of costimulatory molecules but lower levels of the cosuppressor molecule ICOS-L and started production of IL-12/23p40 and TNF-α. Furthermore, we noted that kidney dendritic cells captured more filterable antigen in proteinuric mice at late time points of nephrotoxic nephritis and started to capture molecules that were too large for filtration by a healthy kidney. They presented filtered antigen to Th cells, which responded by producing the proinflammatory cytokines IL-2, IFN-γ, TNF-α, IL-6, and IL-17. Notably, production of the suppressive cytokine IL-10 further increased in late nephrotoxic nephritis. Depletion of kidney dendritic cells at a late stage attenuated nephrotoxic nephritis, in contrast to the exacerbation observed with depletion at an early stage, indicating that their acquired proinflammatory phenotype adversely affected disease. These findings indicate that the intrarenal inflammatory microenvironment determines how kidney dendritic cells affect nephritis. In addition, proteinuria may harm the kidney by providing dendritic cells with more antigens to stimulate potentially pathogenic Th cells.
authors.affiliation: Institute of Experimental Immunology (IMMEI), Friedrich-Wilhelms-Universität, 53105 Bonn, Germany. ckurts@web.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Hochheiser
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Engel
authors.forename: Linda
authors.initials: L
authors.lastname: Hammerich
authors.forename: Felix
authors.initials: F
authors.lastname: Heymann
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology*; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology*; D007668:Kidney / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000941:Antigens