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. Conclusion: Th17/IL-17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing podocyte apoptosis.

Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

“…6B, C). Similarly, it was reported that rIL-17 also promoted podocyte apoptosis, and increased caspase 3 in cultured podocytes [25]. Here, phalloidin staining displayed that rIL-17 also caused disorganization of actin cytoskeleton in cultured podocytes, evidenced by the disappearance of actin filamentous and the induction of actin nucleation (Fig.…”

“…Immunoblotting assay showed that rIL-17 led to a slight reduction of total nephrin. Nevertheless, it was reported that the same dose of rIL-17 had no effect on the expression of nephrin, but resulted in a decreased expression of another podocyte protein podocalyxin in cultured podocytes [25]. Importantly, phosphor-nephrin level was measured here by quantitative immunoblotting assay, and our data show a dramatic reduction of phosphor-nephrin by rIL-17 (Fig.…”

“…4A). In human patients with MCNS, mesangial proliferative glomerulonephritis (MsPGN) or Focal segmental glomerulosclerosis (FSGS), immunohistochemistry staining showed that the intensity of IL-17 increased as well in renal biopsy tissue [25]. To explore whether IL-17R was induced in AN mice, mouse glomeruli was isolated by using a sequential sieving procedure, and the purity about 60% was confirmed under phase contrast microscope (Fig.…”

The Correlation of Regulatory T (TReg) and Vitamin D3 in Pediatric Nephrotic Syndrome

“…Pathogenesis of nephrotic syndrome is based on the immunological aberration, characterized by abundant circulating factor [4] and immuno-regulatory imbalance [5]. Conversely, regulatory T-cells (T Reg ) is an important tolerogenic T-cell possessing protective effect on podocyte destruction [6,7].…”

Th17/Treg cell expression in children with primary nephritic syndrome and the effects of ox-LDL on Th17/Treg cells

“…This disease can frequently recur in patients once it progresses to later stages, which can in severe cases lead to chronic glomerular sclerosis (Paul et al, 2014; Working Group for National Survey on Status of Diagnosis and Treatment of Childhood Renal Diseases, 2014; Ezaki et al, 2015;Geng et al, 2015;Chen and Xia, 2015;Yang and Zhang, 2015). CD4+ cells can be classified into T helper cell 1 (Th1), Th2, Th17, and CD4+CD25+ regulatory cells (Treg) in vitro (Wang et al, 2010(Wang et al, , 2013. Physiologically, there is a relatively stable dynamic equilibrium between Th17 and Treg cells, which is an antagonistic relationship.…”