IL‐17A produced by both γδ T and Th17 cells promotes renal fibrosis via RANTES‐mediated leukocyte infiltration after renal obstruction. Issue 1 (6th October 2014)

• Record Type: Journal Article
• Authors: Peng, Xiaogang; Xiao, Zhicheng; Zhang, Jing; Li, Yulin; Dong, Yanjun; Du, Jie
• Is Part Of: Journal of pathology. Volume 235:Issue 1(2015)
• Page Start: 79
• Page End: 89
• Publication Date: 2014-10-06
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4430
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4430-abs-0001"> <title>Abstract</title> <p id="path4430-para-0001">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 <italic>γδ</italic> 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 © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd</p> </abstract>