کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6087007 | 1589427 | 2016 | 6 صفحه PDF | دانلود رایگان |
- Lupus mice lacking IL-17R were protected from crescentic glomerulonephritis.
- IL-17R is required for the migration of alternatively activated macrophages in the kidney.
- IL-17 regulated the expression of chemokines for renal recruitment of macrophages.
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-17RAâ/â 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.
Journal: Clinical Immunology - Volume 162, January 2016, Pages 31-36