The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome

Shao, Xiao Shan; Yang, Xi; Zhao, Xiao Dong; Li, Qiu; Xie, Yuan; Wang, Xiao Gang; Wang, Mo; Zhang, Wei

doi:10.1007/s00467-009-1194-x

Cited by 89 publications

(88 citation statements)

References 25 publications

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“…16 Emerging evidence suggests that Th17/Treg imbalances contributes to the development of autoimmune diseases, such as SLE 17 and primary nephrotic syndrome. 18 We and others have previously demonstrated that Th17 cells were elevated and numbers and/or function of Treg cells were suppressed in the peripheral blood of ITP patients, [19][20][21][22] indicating a vital role of Th17/Treg imbalances in the pathogenesis of ITP. However, the molecular mechanisms that underline the Th17/Treg imbalances in ITP remain unknown.…”

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confidence: 89%

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Liu

et al. 2015

Laboratory Investigation

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T helper 17 (Th17) cells and regulatory T (Treg) cells, along with Th1 and Th2 cells, may contribute to the development of immune thrombocytopenia (ITP). The imbalance of Th17/Treg toward Th17 cells has been shown to play a pivotal role in the peripheral immune response. Notch signaling has been implicated in peripheral T-cell activation and effector cell differentiation. However, the role of Th17/Treg in the pathogenesis of ITP and the effect of Notch signaling on Th17/Treg imbalances remain largely elusive in ITP. In vitro, we treated peripheral blood mononuclear cells (PBMCs) from ITP and healthy controls with g-secretase inhibitor (DAPT). Th17 cells and Treg cells were measured by flow cytometry and IL-17, IL-21, and IL-10 secretion by enzyme immunoassay technique. The mRNA expression of Ntoch1, Hes1, Hey1, RORgt, and Foxp3 was investigated by RT-PCR. Cell proliferation and apoptosis were determined by the Cell Counting Kit-8 and apoptosis detection kit. We demonstrated that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. In untreated cultured PBMCs from ITP patients, we observed elevated Th17 cell and IL-21 levels and RORgt mRNA expression, decreased Treg cells and Foxp3 mRNA expression, and an increased ratio of Th17/Treg and RORgt/Foxp3. After inactivating Notch signal by DAPT, Th17 cells and Th17/Treg ratio were dose dependently decreased and accompanied by the reduction of IL-17 in culture supernatants and RORgt mRNA expression in ITP patients. However, no significant difference was found for Treg cells and Foxp3 mRNA expression, RORgt/Foxp3 ratio, and IL-21 and IL-10 levels after DAPT treatment in ITP patients. We also present evidence that the effect of DAPT inhibition on the Th17 cell response was associated with downregulation of RORgt and IL-17 transcription using human in vitro polarization. In conclusion, our findings highlight the importance of Notch signaling in Th17/Treg imbalances in ITP. Inactivation of Notch signaling might be a potential immunoregulatory strategy in ITP patients.

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confidence: 89%

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Liu

et al. 2015

Laboratory Investigation

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“…More recently, the Th17 cell, which secretes factors such as IL-17, L-22, and IL-23, was discovered and implicated in the pathogenesis of inflammatory and autoimmune diseases. Shao [8] and our preliminary experiments suggest that Th17 and related factors may take part in the leakage of proteinura in PNS, but its mechanism is still unknown.…”

Section: Introductionmentioning

confidence: 99%

The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children

Wang

et al. 2013

Kidney Blood Press Res

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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.

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“…Experimental animal studies suggest that Treg cells can reduce the urinary protein content in focal segmental glomerular sclerosis (FSGS) rats, and play a protective role in graft rejection nephritis (Gorantla et al, 2010). Shao et al (2009) believed that Th17 and Treg cells have an obvious effect on the maintenance of inflammatory and immune homeostasis. Reducing Treg cells and increasing Th17 cells can lead to the incidence of renal allograft rejection, lupus nephropathy, immunoglobulin A(IgA) nephropathy, hyperplasia of glomerular nephritis, nephritis, acute coronary comprehensive syndrome, allergic purpura, and other diseases (Turner et al, 2010;Yu et al, 2013;ZambranoZaragoza et al, 2014;Feng et al, 2015;Tabarkiewicz et al, 2015) .…”

Section: Discussionmentioning

confidence: 99%

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

Wei

Zhao

et al. 2016

Genet. Mol. Res.

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ABSTRACT.To investigate the role of T-helper cells/Treg (Th17/ Treg) and morbidity factors related to primary nephritic syndrome (PNS) in children, as well as the influence of ox-low density lipoprotein (ox-LDL) on Th17/Treg expression in children with PNS. To clarify the pathogenesis of PNS in children, 50 children with PNS treated in our hospital were enrolled in the study group. Additionally, 20 healthy children who came to our hospital for physical examination during the same period were enrolled in the control group. Th17 and Treg cells in children belonging to the two groups were detected by flow cytometry; the numbers of Th17/Treg cells in peripheral blood mononuclear cells at different concentrations of ox-LDL were detected simultaneously. Ox-LDL can affect the number of Th17/Treg cells in peripheral blood mononuclear cells, and both cell types decreased with increasing concentration of ox-LDL, with the numbers being significantly lower in the control group. However, the decrease in the number of Th17 cells was statistically insignificant (P > 0.05), whereas the decrease in Treg cells was more obvious and statistically significant (P < 0.05). The effect of ox-LDL the number of Treg cells was stronger than that on Th17 cells. We concluded that the imbalance of Th17/Treg cells influenced by high and low ox-LDL concentrations in children with PNS might be the immunological basis of the disease.

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The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome

Cited by 89 publications

References 25 publications

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children

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

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