Skip to main content
Top
Published in: Pediatric Nephrology 9/2009

01-09-2009 | Original Article

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

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

Published in: Pediatric Nephrology | Issue 9/2009

Login to get access

Abstract

The aim of this study was to investigate the prevalence of interleukin (IL)-17-producing CD4+ T cells (Th17) and regulatory T (Treg) cells in children with primary nephrotic syndrome. The study cohort consisted of 62 children who were randomly divided into control, primary nephrotic syndrome, and isolated hematuria groups. Flow cytometric analysis revealed the presence of Th17 cells in the peripheral blood mononuclear cells (PBMCs) of 35 children and Tregs in the PBMCs of all children. In addition, mRNA expression of Th17-related factors [IL-17, -23p19 and retinoid orphan nuclear receptor (RORc)] and the concentration of plasma inflammatory mediators such as IL-6 and IL-1β were consistently detected in all children. Protein expression of IL-17 and transforming growth factor-β1 were also detected in renal biopsy tissue and compared between different groups. Patients with PNS were found to have an increased number of Th17 cells and decreased numbers of Tregs in their PBMCs, and there was significant difference in the prevalence of Th17 and Tregs between the patients with PNS and those with isolated hematuria. Our data show that among our study cohort, there was a dynamic equilibrium between Th17 and Treg cells in children with PNS following the development of PNS with apparent renal tubular epithelial cell and interstitium lesions. The dynamic interaction between Th17 and Treg cells may be important in the development of PNS.
Literature
1.
go back to reference Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin-17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1069–1070CrossRef Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin-17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1069–1070CrossRef
2.
go back to reference Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238CrossRef Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238CrossRef
3.
go back to reference Dong C (2006) Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat Rev Immunol 6:329–333CrossRef Dong C (2006) Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat Rev Immunol 6:329–333CrossRef
4.
go back to reference Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor beta induces development of the T(H) 17 lineage. Nature 441:231–234CrossRef Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor beta induces development of the T(H) 17 lineage. Nature 441:231–234CrossRef
5.
go back to reference Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467CrossRef Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467CrossRef
6.
go back to reference Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348CrossRef Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348CrossRef
7.
go back to reference Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor ROR gammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–1133CrossRef Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor ROR gammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–1133CrossRef
8.
go back to reference McGeachy MJ, Cua DJ (2008) Th17 cell differentiation: the long and winding road. Immunity 28:445–453CrossRef McGeachy MJ, Cua DJ (2008) Th17 cell differentiation: the long and winding road. Immunity 28:445–453CrossRef
9.
go back to reference Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-β1eta are required for differentiation of human T(H) 17 cells. Nature 454:350–352CrossRef Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-β1eta are required for differentiation of human T(H) 17 cells. Nature 454:350–352CrossRef
10.
go back to reference Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9:650–657CrossRef Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9:650–657CrossRef
11.
go back to reference Manel N, Unutmaz D, Littman DR (2008) The differentiation of human TH-17 cells requires transforming growth factor-b and induction of the nuclear receptor RORct. Nat Immunol 9:641–649CrossRef Manel N, Unutmaz D, Littman DR (2008) The differentiation of human TH-17 cells requires transforming growth factor-b and induction of the nuclear receptor RORct. Nat Immunol 9:641–649CrossRef
12.
go back to reference Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476CrossRef Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476CrossRef
13.
go back to reference Bettelli E, Oukka M, Kuchroo VK (2007) TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350CrossRef Bettelli E, Oukka M, Kuchroo VK (2007) TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350CrossRef
14.
go back to reference Chen X, Vodanovic-Jankovic S, Johnson B, Keller M, Komorowski R, Drobyski WR (2007) Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versushost disease. Blood 110:3804–3813CrossRef Chen X, Vodanovic-Jankovic S, Johnson B, Keller M, Komorowski R, Drobyski WR (2007) Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versushost disease. Blood 110:3804–3813CrossRef
15.
go back to reference Kiliś-Pstrusińska K, Zwolińska D, Medyńska A, Wawro A, Kordecki H (2006) Interleukin-17 concentration in serum and urine of children with idiopathic nephrotic syndrome. Przegl Lek 63:198–200PubMed Kiliś-Pstrusińska K, Zwolińska D, Medyńska A, Wawro A, Kordecki H (2006) Interleukin-17 concentration in serum and urine of children with idiopathic nephrotic syndrome. Przegl Lek 63:198–200PubMed
16.
go back to reference Matsumoto K, Kanmatsuse K (2002) Increased urinary excretion of interleukin-17 in nephrotic patients. Nephron 91:243–249CrossRef Matsumoto K, Kanmatsuse K (2002) Increased urinary excretion of interleukin-17 in nephrotic patients. Nephron 91:243–249CrossRef
17.
go back to reference Rizk MK, El-Nawawy A, Abdel-Kareem E, Amer ES, El-Gezairy D, El-Shafei AZ (2005) Serum interleukins and urinary microglobulin in children with idiopathic nephrotic syndrome. East Mediterr Health J 11:993–1002PubMed Rizk MK, El-Nawawy A, Abdel-Kareem E, Amer ES, El-Gezairy D, El-Shafei AZ (2005) Serum interleukins and urinary microglobulin in children with idiopathic nephrotic syndrome. East Mediterr Health J 11:993–1002PubMed
18.
go back to reference Qin J, Zhang Z, Liu J, Sun L, Hu L, Cooper ME, Cao Z (2003) Effects of the combination of an angiotensin II antagonist with an HMG-CoA reductase inhibitor in experimental diabetes. Kidney Int 64:565–571CrossRef Qin J, Zhang Z, Liu J, Sun L, Hu L, Cooper ME, Cao Z (2003) Effects of the combination of an angiotensin II antagonist with an HMG-CoA reductase inhibitor in experimental diabetes. Kidney Int 64:565–571CrossRef
19.
go back to reference Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560CrossRef Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560CrossRef
20.
go back to reference Afzali B, Lombardi G, Lechler RI, Lord GM (2007) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 148:32–46CrossRef Afzali B, Lombardi G, Lechler RI, Lord GM (2007) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 148:32–46CrossRef
21.
go back to reference Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+CD25−naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886CrossRef Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+CD25−naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886CrossRef
22.
go back to reference Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–260CrossRef Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–260CrossRef
23.
go back to reference Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, de Waal Malefyt R (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957CrossRef Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, de Waal Malefyt R (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957CrossRef
24.
go back to reference Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56:2936–2946CrossRef Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56:2936–2946CrossRef
25.
go back to reference Alvarez V, Quiroz Y, Nava M, Pons H, Rodríguez-Iturbe B (2002) Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells. Am J Physiol Renal Physiol 283:1132–1141CrossRef Alvarez V, Quiroz Y, Nava M, Pons H, Rodríguez-Iturbe B (2002) Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells. Am J Physiol Renal Physiol 283:1132–1141CrossRef
26.
go back to reference Homey B (2006) After TH1/TH2 now comes Treg/TH17: significance of T helper cells in immune response organization. Hautarzt 57:730–732CrossRef Homey B (2006) After TH1/TH2 now comes Treg/TH17: significance of T helper cells in immune response organization. Hautarzt 57:730–732CrossRef
Metadata
Title
The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome
Authors
Xiao Shan Shao
Xi Qang Yang
Xiao Dong Zhao
Qiu Li
Yuan Yuan Xie
Xiao Gang Wang
Mo Wang
Wei Zhang
Publication date
01-09-2009
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 9/2009
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-009-1194-x

Other articles of this Issue 9/2009

Pediatric Nephrology 9/2009 Go to the issue