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IL‐17A produced by both γδ T and Th17 cells promotes renal fibrosis via RANTES ‐mediated leukocyte infiltration after renal obstruction
Author(s) -
Peng Xiaogang,
Xiao Zhicheng,
Zhang Jing,
Li Yulin,
Dong Yanjun,
Du Jie
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4430
Subject(s) - chemokine , fibrosis , infiltration (hvac) , interleukin 17 , kidney , inflammation , pathogenesis , extracellular matrix , medicine , myofibroblast , immunology , pathology , biology , endocrinology , microbiology and biotechnology , materials science , composite material
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 γδ 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 & Sons, Ltd