title: Renal IL-17 expression in human ANCA-associated glomerulonephritis.
abstract: Interleukin-17A (IL-17) promotes inflammatory renal tissue damage in mouse models of crescentic glomerulonephritis, including murine experimental autoimmune anti-myeloperoxidase glomerulonephritis, which most likely depends on IL-17-producing Th17 cells. In human anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, however, the cellular sources of IL-17 remain to be elucidated. Therefore, we analyzed human kidney biopsies of active necrotizing and crescentic ANCA-associated glomerulonephritis by immunohistochemistry using an IL-17-specific antibody and by immunofluorescent colocalization with cell type markers. We detected numerous IL-17-expressing (IL-17(+)) cells in the glomeruli and in the tubulointerstitium. Unexpectedly, most of these IL-17(+) cells were polymorphonuclear neutrophilic granulocytes, while IL-17(+) T cells and IL-17(+) mast cells were present at significantly lower frequencies. IL-17 was not detected in other infiltrating or resident kidney cells. In those patients who had not received immunosuppressive treatment before biopsy, serum creatinine levels were positively correlated with tubulointerstitial IL-17(+) neutrophils as well as IL-17(+) T cells. Furthermore, we could demonstrate that purified human blood neutrophils expressed IL-17 protein and released it upon stimulation in vitro. In conclusion, these results support a pathogenic role for IL-17 in human ANCA-associated glomerulonephritis. Our data suggest that in the acute stage of the disease neutrophils may act as an important immediate-early innate source of IL-17 and may thereby initiate and promote ongoing renal inflammation. IL-17 may thus be a target for treating acute ANCA-associated glomerulonephritis.
authors.affiliation: Nierenregister, Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. joachim.velden@uk-erlangen.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.forename: Elion
authors.initials: E
authors.lastname: Hoxha
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
authors.forename: Wolfram J
authors.initials: WJ
authors.lastname: Jabs
authors.forename: Fedai
authors.initials: F
authors.lastname: Özcan
authors.forename: Joachim
authors.initials: J
authors.lastname: Beige
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Heering
authors.forename: Saskia
authors.initials: S
authors.lastname: Schröder
authors.forename: Ursula
authors.initials: U
authors.lastname: Kneißler
authors.forename: Erik
authors.initials: E
authors.lastname: Disteldorf
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D020381:Interleukin-17