title: The role of Th17/IL-17 in the pathogenesis of primary nephrotic syndrome in children.
abstract: BACKGROUND
  This work aims to explore the role of Th17 and IL-17 signaling in the pathogenesis of primary nephrotic syndrome (PNS) in children and podocyte injury, children with PNS were divided into minimal change nephrotic syndrome (MCNS) and non-minimal change nephrotic syndrome [NMCNS, including mesangial proliferative glomerulonephritis (MsPGN) and focal segmental glomerulosclerosis (FSGS)].
  
  
  METHODS
  Flow cytometry (FCM) was used to observe the circulating frequency of Th17 cells and the apoptosis of podocytes by annexinV-FITC/PI. Serum IL-1β and IL-6 levels were measured using enzyme-linked immunosorbent assay. The Fas and FasL expressions in podocytes were examined by FCM analysis using a direct immunofluorescence method. Reverse transcription polymerase chain reaction was applied to measure the mRNA expressions of RORc, IL-23p19, Nephrin, WT1, Synaptopodin, Podocalyxin, Fas, and FasL. The IL-17 and IL-1β expression in renal biopsy tissue was detected by immunohistochemistry. The expressions of WT1, Caspase 8, and Caspase 3 in podocyte cell culture were also measured using immunocytochemistry.
  
  
  RESULTS
  Circulating frequencies of Th17 cells, mRNA levels of RORc and IL-23p19, and serum levels of IL-6 and IL-1β were higher in the MCNS and NMCNS groups than in the control group (all P < 0.05), and were higher in the NMCNS group than in the MCNS group (all P < 0.05). The expressions of IL-17 and IL-1β in renal biopsy tissue were higher in the MCNS, MsPGN, and FSGS groups than in the control group (all P < 0.05). Recombinant murine IL-17 (rmIL-17) had no effect on the expressions of Nephrin, Synaptopodin, and WT1 of mouse podocytes, but caused an decrease in the expression of podocalyxin as well as promoted apoptosis in a dose- and time-dependent fashion. Moreover, rmIL-17 increased the expression of Fas, Casepase-8, and Casepase-3, but had no effect on that of FasL.
  
  
  CONCLUSIONS
  Th17/IL-17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing podocyte apoptosis.
authors.affiliation: Department of Nephroimmunology, Children's Hospital of Chongqing Medical University, Chongqing 400014, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Lijia
authors.initials: L
authors.lastname: Wang
authors.forename: Cuicui
authors.initials: C
authors.lastname: Li
authors.forename: Haiping
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D050199:Podocytes / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*
chemical_list: D020381:Interleukin-17