title: Interleukin 17 signaling drives Type I Interferon induced proliferative crescentic glomerulonephritis in lupus-prone mice.
abstract: Crescentic glomerulonephritis (cGN) is a severe clinical manifestation in a subset of patients with Systemic lupus erythematosus. Lack of understanding of the pathogenesis of cGN act as a major constraint in treating these patients. Emerging evidence suggest a critical role of IL-17 in the pathogenesis of membranoproliferative glomerulonephritis in lupus. However, the role of IL-17 receptor (IL-17RA) signaling in cGN is unknown. Here, we developed a model of poly I:C-induced Type I Interferon (IFN-I)-dependent cGN in B6.MRL-Faslpr/J (B6.lpr) mice. B6.lpr mice deficient in IL-17RA were protected from IFN-I-dependent cGN. While systemic response was unabated, renal infiltration of alternatively activated macrophages was severely impaired in IL-17RA(-/-) mice. Finally, we show that IL-17 differentially regulates the expression of macrophage chemo-attractant genes in renal tubular epithelial cells and macrophages in association with IFN-I. These results suggest that neutralization IL-17 may confer better protection in SLE patients with high IFN-I gene signature and cGN.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Kritika
authors.initials: K
authors.lastname: Ramani
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: psb13@pitt.edu.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Biswas
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D020381:Interleukin-17 / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008181:Lupus Nephritis / Q000503:physiopathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: C508717:IL17A protein, human; D007370:Interferon Type I; D020381:Interleukin-17
keywords: Crescentic glomerulonephritis; IL-17; Lupus; Systemic lupus erythematosus; Type I Interferon