title: IL-17A produced by both γδ T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction.
abstract: 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.
authors.affiliation: Beijing AnZhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases. The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Peng
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D018946:Chemokine CCL5 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D005355:Fibrosis; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D018925:Chemokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: IL-17A; RANTES; inflammation; obstructive nephropathy; renal fibrosis