title: The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis.
abstract: T cells infiltrate the kidney in both human and experimental glomerulonephritis, and several lines of evidence indicate that T cell-mediated tissue damage plays an important role in the immunopathogenesis of renal inflammatory diseases. However, the functions of the different T cell subsets, particularly the recently identified interleukin-17 (IL-17)-producing T cells (Th17 cells), are incompletely understood in glomerulonephritis. Here, we identified renal IL-17-producing T cells in the T cell-mediated model of nephrotoxic nephritis in mice. In vitro, IL-17 enhanced the production of the proinflammatory chemokines CCL2/MCP-1, CCL3/MIP-1alpha, and CCL20/LARC, which are implicated in the recruitment of T cells and monocytes, in mouse mesangial cells. To determine the function of Th17 cells in renal inflammation, we induced nephrotoxic nephritis in IL-23 p19(-/-) mice, which have reduced numbers of Th17 cells, and in IL-17(-/-) mice, which are deficient in the effector cytokine IL-17 itself. In comparison with nephritic wild-type mice, IL-23 p19(-/-) mice demonstrated less infiltration of Th17 cells, and both IL-23 p19(-/-) and IL-17(-/-) mice developed less severe nephritis as measured by renal function, albuminuria, and frequency of glomerular crescent formation. These results demonstrate that the IL-23/IL-17 pathway significantly contributes to renal tissue injury in experimental glomerulonephritis. Targeting the IL-23/Th17 axis may be a promising therapeutic strategy for the treatment of proliferative and crescentic glomerulonephritis.
authors.affiliation: Universitätsklinikum Hamburg-Eppendorf, III Medizinische Klinik, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.forename: Anett
authors.initials: A
authors.lastname: Peters
authors.forename: Felix
authors.initials: F
authors.lastname: Heymann
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer