The role of Th17/IL-17 in the pathogenesis of primary nephrotic syndrome in children.

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-1 beta 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-1 beta 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-1 beta 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-1 beta 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. Conclusion: Th17/IL-17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing podocyte apoptosis. Copyright (C) 2013 S. Karger AG, Basel