An essential role of interleukin-17 receptor signaling in the development of autoimmune glomerulonephritis. Issue 3 (16th June 2014)

• Record Type: Journal Article
• Authors: Ramani, Kritika; Pawaria, Sudesh; Maers, Kelly; Huppler, Anna R; Gaffen, Sarah L; Biswas, Partha S
• Is Part Of: Journal of leukocyte biology. Volume 96:Issue 3(2014)
• Page Start: 463
• Page End: 472
• Publication Date: 2014-06-16
• Subjects: IL-17 -- inflammation -- kidney; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0414-184R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Blocking IL-17R signaling may be a promising therapeutic strategy for the treatment of proliferative and crescentic glomerulonephritis. Abstract: 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.