IL-17A produced by both δ T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction

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• 作者：Xiaogang Peng ; Zhicheng Xiao ; Jing Zhang ; Yulin Li ; Yanjun Dong and Jie Du
• 关键词：IL-17A ; RANTES ; renal fibrosis ; inflammation ; obstructive nephropathy
• 刊名：The Journal of Pathology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：235
• 期：1
• 页码：79-89
• 全文大小：3387K
• ISSN：1096-9896

文摘

IL-17A-producing T lymphocytes play a crucial role in inflammatory kidney diseases, but their role in renal fibrosis remains to be explored. Here, we demonstrated that up-regulation of IL-17A was associated with the development of obstructive kidney injury. The primary source of IL-17A production in obstructed kidneys was infiltrating δ T lymphocytes and CD4⁺ T cells. IL-17A-deficient mice were protected from myofibroblast activation and extracellular matrix deposition, leading to reduced kidney fibrosis in response to obstructive injury. Mechanistically, IL-17A deficiency suppressed the expression of the chemokine RANTES in infiltrated CD3⁺ T cells and peritubular inflammation following renal obstruction. Administration of RANTES-neutralizing antibody significantly reduced the accumulation of T cells and macrophages, and of collagen deposition in obstructed kidneys. Taken together, our results indicate that IL-17A contributes significantly to the pathogenesis of renal fibrosis by regulating RANTES-mediated inflammatory cell infiltration. Copyright