title: Hemolytic Streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20 response to the effect of Th17 cells.
abstract: BACKGROUND
  The exacerbation of IgA nephropathy (IgAN) is related to respiratory tract infection with hemolytic streptococcus (HS), but the mechanism is unknown. In this study we investigated the role of chemokine ligand 20 (CCL20) in response to the effect of T helper 17 (Th17) cells in the pathogenesis of IgAN associated with HS.
  
  
  METHODS
  Thirty mice were randomly divided into five groups: control mice (control), IgAN mice (IgAN), HS-infected IgAN mice (HS-IgAN), CCL20-treated IgAN mice (CCL20-IgAN), and CCL20-treated HS infected IgAN mice (CCL20-HS-IgAN). IgAN mice were induced with lipopolysaccharide, carbon tetrachloride and bovine serum albumin. Then the mice were sensitized with CCL20 antibody and infected with alpha-hemolytic streptococcus (α-HS) isolated from tonsils in sequence. Urine Albumin-Creatinine ratio and sediments were measured. The pathological changes in kidney and lung tissues were observed under microscopy. Th17 cells and regulatory T cells (Tregs) in kidneys were tested by flow cytometry. CCL20, IL-17A, IL-6 and IL-21 in the kidneys were detected by ELISA.
  
  
  RESULTS
  The IgAN mice had albuminuria and microscopic hematuria, renal mesangial proliferation, IgA deposition, high electron dense deposition in glomerular mesangial region, decreased frequency of Tregs, increased frequency of Th17 and Th17-Treg ratio. Furthermore, Th17-related cytokines CCL20, IL-17A, IL-6 and IL-21 were all increased in the kidneys of IgAN mice. Compared with IgAN mice, the manifestations in HS-IgAN mice were more severe, but alleviated in CCL20-treated groups.
  
  
  CONCLUSIONS
  α-HS may exacerbate kidney damage in IgAN through CCL20 response to the effect of Th17 cells.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Meng
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zou
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054418:Chemokine CCL20 / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D013291:Streptococcus / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D000418:Albumins; D000906:Antibodies; D054418:Chemokine CCL20; D003404:Creatinine