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Renal IL-17 expression in human ANCA-associated glomerulonephritis.
MedLine Citation:
PMID:  22442208     Owner:  NLM     Status:  Publisher    
Interleukin-17A (IL-17) promotes inflammatory renal tissue damage in mouse models of crescentic glomerulonephritis, including murine experimental autoimmune anti-MPO glomerulonephritis, which most likely depends on IL-17 producing Th17 cells. In human 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 co-localization 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.
Joachim Velden; Hans-Joachim Paust; Elion Hoxha; Jan-Eric Turner; Oliver M Steinmetz; Gunter Wolf; Wolfram J Jabs; Fedai Ozcan; Joachim Beige; Peter J Heering; Saskia Schröder; Ursula Kneissler; Erik Disteldorf; Hans-Willi Mittrücker; Rolf Ak Stahl; Udo Helmchen; Ulf Panzer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-21
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Universitaetsklinikum Hamburg-Eppendorf.
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