An essential role of interleukin-17 receptor signaling in the development of autoimmune glomerulonephritis. J Leukoc Biol 2014 Sep;96(3):463-72
Date
06/18/2014Pubmed ID
24935958Pubmed Central ID
PMC4138200DOI
10.1189/jlb.3A0414-184RScopus ID
2-s2.0-84907329820 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
In recent years, proinflammatory cytokines in the nephritic kidney appear to contribute to the pathogenesis of AGN. The complex inflammatory cytokine network that drives renal pathology is poorly understood. IL-17, the signature cytokine of Th17 cells, which promotes autoimmune pathology in a variety of settings, is beginning to be identified in acute and chronic kidney diseases as well. However, the role of IL-17-mediated renal damage in the nephritic kidney has not been elucidated. Here, with the use of a murine model of experimental AGN, we showed that IL-17RA signaling is critical for the development of renal pathology. Despite normal systemic autoantibody response and glomerular immune-complex deposition, IL-17RA(-/-) mice exhibit a diminished influx of inflammatory cells and kidney-specific expression of IL-17 target genes correlating with disease resistance in AGN. IL-17 enhanced the production of proinflammatory cytokines and chemokines from tECs. Finally, we were able to show that neutralization of IL-17A ameliorated renal pathology in WT mice following AGN. These results clearly demonstrated that IL-17RA signaling significantly contributes to renal tissue injury in experimental AGN and suggest that blocking IL-17RA may be a promising therapeutic strategy for the treatment of proliferative and crescentic glomerulonephritis.
Author List
Ramani K, Pawaria S, Maers K, Huppler AR, Gaffen SL, Biswas PSAuthor
Anna H. Huppler MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Glomerular Basement Membrane Disease
CD4-Positive T-Lymphocytes
Cells, Cultured
Chemotaxis, Leukocyte
Cytokines
Drug Synergism
Epithelial Cells
Female
Interleukin-17
Kidney Tubules
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
RNA, Messenger
Receptors, Interleukin-17
Signal Transduction
Specific Pathogen-Free Organisms
Tumor Necrosis Factor-alpha
Up-Regulation
