| Background and Objective: Primary nephrotic syndrome(PNS)is the most prevalent kidney disease in children and is a main cause of chronic renal failure in children in China.Clinical characteristics of PNS include increased permeability of the glomerular filtration barrier,which leads to proteinuria,hypoalbuminaemia and oedema.To date,the underlying pathogenesis of PNS remains largely unknown.Some researchers hypothesize that PNS may be caused by dysregulation of T lymphocytes or an abnormal T cell response.Evidence suggests that an imbalance of Th1/Th2 cells and Th17/Treg cells is present in patients with PNS.However,the molecular mechanism underlying the imbalance in these Th cell subsets in children with PNS is not fully understood.??T cells are a minor population of T cells that express the ? and ?chains of the T cell receptor(TCR).??T cells account for approximately1–5% of circulating T cells in blood.In contrast to conventional ?? T cells,??T cells can recognize antigens in a major histocompatibility complex(MHC)-unrestricted manner,and sense cellular stress and infection.Human??T cells are able to participate in both the innate and adaptive immuneresponse and are important for optimal differentiation of Th17 cells,suppressing Treg cell responses,and directing the immune response to the Th1-or Th2-phenotype.Many studies indicate ??T cells play pivotal roles in immunity against infection,cancer and autoimmune diseases.Therefore,??T cells may link innate and adaptive immunity,which could play a crucial role in regulating the CD4+ T cell immune response.??T cells have also been studied in renal injury.Mice deficient in ??T cells developed minimal proteinuria and glomerular lesions in a nephrotoxic nephritis model.IL-17 A production by renal ??T cells may promote kidney injury in crescentic glomerulonephritis,and histologic analyses demonstrated a significant reduction in renal tubular injury in TCR ??-deficient mice compared to wildtype mice in a renal ischaemia–reperfusion model.Other studies indicate that ??T cells are important for immune regulation in kidney disease.A gradual increase in ??T cells was observed in mice kidneys after intrarenal inoculation with Listeria monocytogenes,while depletion of ??T cells in vivo resulted in histologically exacerbated inflammation in the kidneys.Furthermore,high levels of ??T cells and TGF-? were found in models of active heymann nephritis or adriamycin-induced progressive renal failure.Evidence suggests that ??T cells are involved in the progression of Ig A nephropathy to renal failure.However,little is known about the role of??T cells in PNS.The objective of this study was to explore the effect and mechanism of action of ??T cells and ??T cell subsets in modulating the balance between Th17 cells and Treg cells from peripheral blood mononuclear cells(PBMCs)in paediatric PNS.Our previous study showed that m RNA expression of ROR? and IL-23p19 was higher in PBMC and the number of circulating Th17 cells was increased on children with PNS compared to a healthy group.Therefore,we hypothesized that IL-23 could play an important role in PNS.As IL-21 is one cytokine secreted by Th17,it is also investigated in this study.PART ? Effect of ??T cells on Th17/Treg balance in children with PNSObjective: To investigate the level and function of ??T cells?IL-23R+??T cells?IL-17+??T cells in peripheral blood of children with Simple primary nephrotic syndrome(SNS)and the effects of which on the immune balance of Th17/Treg.Methods: A total of 64 children with SNS were collection,of which acute period of active simple nephrotic syndrome(SNS)in 51 cases,13 simple nephrotic syndrome in remission(RM-SNS),21 cases(Control)of peripheral blood were collected from healthy physical examination children.Using flow cytometry to detect the percentage of ??T cells?IL-23R+ ??T cells?IL-17+??T cells?Th17 and Treg in the peripheral blood.Further analysis of correlation of ??T cells?IL-23R+ ??T cells and IL-17+??T cells between Th17 cells and Treg cells.Results: Compared with the control group,the proportion of Th17 cells in SNS group were remarkably increased(P < 0.05),and the proportion of Treg cells were remarkably decreased(P < 0.05),the Th17/Treg ratio was increased significantly(P < 0.05).The proportion of Th17 ? Treg and the Th17/Treg ratio in RM-SNS group didn't show significant difference compared to those in control group.Compared with control group,the percentage of ??T cells?IL-23R+ ??T cells and IL-17+??T cells in SNS group were significantly increased(P <0.05);while the percentage of ??T cells and IL-17+??T cells were no significantly different in RM-SNS group(P > 0.05).However,the percentage of IL-23R+ ??T cells in RM-SNS group still significantly increased than control group(P>0.05).Compared with SNS group,the percentage of ??T cells and IL-17+??T cells in RM-SNS group were significantly decreased(P < 0.05).However,the percentage of IL-23R+ ??T cells in RM-SNS group had decreased than the active SNS group,but there was no significant difference(P>0.05).Our results demonstrate a significant positive correlation between ??T cells,IL-23R+ ??T cells,IL-17+??T cells and Th17 cells in the peripheralblood in children with PNS.There were a significant positive correlation between ??T cells,IL-23R+ ??T cells,IL-17+??T cells and the ratio of Th17/Treg(P < 0.05),and the IL-23R+ ??T cells showed a negative correlation with Treg(P < 0.05).Conclusion: ??T cells and its two subsets may play an important role in the development of SNS through affecting the balance of Th17/TregPART ? IL-23-??T-Th17/Treg axis is involved in the development and prognosis of PNSObjective: To investigate that ??T cells play a role in the development and prognosis of SNS probably by regulating the Th17/Treg balance.Methods:Peripheral blood mononuclear cells of patients were cultured.Cultures were divided into four groups :(1)Control group(2)IL-23 activating group(3)IL-23 antagonist group(4)anti-IL-21 m Ab group.The percentages of Th17?Treg???T cells?IL-23R+??T cells and the expression of IL-17 and IL-10 were detected with flow cytometry.The relationship between ??T cells or their subsets and the immune balance of Th17 /Tregwas analyzed.Results:Compared to(1)Control group,the percentage of Th17 cells significantly increased(p<0.05)while the percentage of Treg significantly decreased(p<0.05),and immune imbalance of Th17/Treg significantly aggravated(p<0.05)in(2)IL-23 activating group;The percentage of ??T cells significantly increased(p<0.05)and secretion of IL-21 significantly increased(p<0.001),while secretion of IL-17 was not different in(2)IL-23 activating group(p>0.05).Compared to(2)IL-23 activating group,the percentage of Th17 cells significantly decreased(P<0.05),while the percentage of Treg cells significantly increased(P<0.05)in(3)IL-23 antagonist group.The ratio of Th17/Treg significantly decreased(P<0.05);the percentage of ??T cells and IL-21+??T cells significantly decreased in(3)IL-23 antagonist group,while the secretion of IL-17 was not distinct different(p>0.05);the percentage of Th17 and the ratio of Th17/Treg significantly decreased(P<0.05),while the percentage of Treg significantly increased(P<0.05)in(4)anti-IL-21 m Ab group.The percentage of IL-21+??T was not different among(2)and(4)groups(p>0.05).The percentage of IL-17+ ??T cells was not different among the four groups.The percentage of ??T cells was positively correlated with the percentage of Th17 cells following exposure to IL-23.The percentage of ??T cells was negatively correlated with the percentage of Treg cells following exposure to IL-23.The percentage of ??T cells was positively correlated with the Th17 /Treg following exposure to IL-23.The percentage of IL-21+??T cells was positively correlated with the percentage of Th17 cells following exposure to IL-23(P<0.05),as well as Th17/Treg.There was no correlation between IL-17+??T cells and Th17 or Treg.Conclusion: ??T cells may cause an imbalance in Th17/Treg cells by secreting IL-21 in the presence of IL-23.Neutralization of IL-23 and(or)and IL-21 may be the target of new treatment for the treatment of SNS. |
PDF Full Text Request