| First Author | Chan AJ | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 5 | Pages | 1411-8 |
| PubMed ID | 24631024 | Mgi Jnum | J:208397 |
| Mgi Id | MGI:5563258 | Doi | 10.1016/j.ajpath.2014.01.023 |
| Citation | Chan AJ, et al. (2014) Innate IL-17A-Producing Leukocytes Promote Acute Kidney Injury via Inflammasome and Toll-Like Receptor Activation. Am J Pathol 184(5):1411-8 |
| abstractText | In acute kidney injury, which is a significant cause of morbidity and mortality, cytokines and leukocytes promote inflammation and injury. We examined the pathogenic role of IL-17A in cisplatin-induced acute kidney injury. Intrarenal IL-17A mRNA transcription and protein expression were increased in wild-type mice after cisplatin-induced renal injury. An important role for IL-17A in the nephrotoxicity of cisplatin was demonstrated by observing protection from cisplatin-induced functional and histological renal injury in Il17a(-/-) and Rorgammat(-/-) mice, as well as in mice treated pre-emptively with anti-IL-17A antibodies. Both renal injury and renal IL-1beta and IL-17A production were attenuated in Asc(-/-) and Tlr2(-/-) mice, suggesting that cisplatin induces endogenous TLR2 ligand production and activates the ASC-dependent inflammasome complex, resulting in IL-1beta and injurious IL-17A production. Neutrophils and natural killer cells are the likely targets of these pathways, because combined depletion of these cells was strongly protective; anti-IL-17A antibodies had no additional effect in this setting. Although IL-17A can also be produced by CD4(+) and gammadelta T cells, IL-17A from those cells does not contribute to renal injury. Cisplatin-induced injury was unchanged in gammadelta T-cell-deficient mice, whereas Il17a(-/-) CD4(+) T cells induced similar injury as did wild-type CD4(+) T cells on transfer to cisplatin-injected Rag1(-/-) mice. These studies demonstrate an important role for TLR2, the ASC inflammasome, and IL-17A in innate leukocytes in cisplatin-induced renal injury. |
