The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis.
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The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. / Paust, Hans-Joachim; Turner, Jan Eric; Steinmetz, Oliver; Peters, Anett; Heymann, Felix; Hölscher, Christoph; Wolf, Gunter; Kurts, Christian; Mittrücker, Hans Willi; Stahl, Rolf A.K.; Panzer, Ulf.
in: J AM SOC NEPHROL, Jahrgang 20, Nr. 5, 5, 2009, S. 969-979.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis.
AU - Paust, Hans-Joachim
AU - Turner, Jan Eric
AU - Steinmetz, Oliver
AU - Peters, Anett
AU - Heymann, Felix
AU - Hölscher, Christoph
AU - Wolf, Gunter
AU - Kurts, Christian
AU - Mittrücker, Hans Willi
AU - Stahl, Rolf A.K.
AU - Panzer, Ulf
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 20
SP - 969
EP - 979
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 5
M1 - 5
ER -