Skip to main content
Top
Published in: Diagnostic Pathology 1/2019

Open Access 01-12-2019 | Hepatitis B | Research

Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis

Authors: Yong-Ting Lan, Zhen-li Wang, Peng Tian, Xiao-Na Gong, Yu-Chen Fan, Kai Wang

Published in: Diagnostic Pathology | Issue 1/2019

Login to get access

Abstract

Background

Recent studies have shown that T cell-mediated cellular immune mechanisms play important roles in the progression of hepatitis B to liver cirrhosis, but the underlying mechanisms remain unclear. This present study was aimed to determine the relationship between Treg/Th17 and hepatitis B-associated liver cirrhosis.

Methods

The Treg and Th17 cell frequencies in the peripheral blood of all participants, including 93 patients with hepatitis B-associated liver cirrhosis and 40 healthy subjects, were measured by flow cytometer. Cox regression model and receiver operating characteristic(ROC) curves were applied to investigate the prognostic significance of Treg/Th17 ratio in decompensated liver cirrhosis.

Results

We observed the Treg/Th17 imbalance was present in patients with hepatitis B-associated liver cirrhosis, with reduced Treg cells in their peripheral blood, increased Th17 cells and decreased Treg/Th17 ratio. Treg and Th17 cells were negatively correlated. Treg/Th17 imbalance was closely related to the clinical stage of hepatitis B-associated liver cirrhosis. The Virus load, Treg frequencies and the Treg/Th17 ratio were independent factors predicting decompensated liver cirrhosis from a Cox regression model. The ROC analysis showed that the Treg/Th17 ratio was the best marker for predicting decompensated liver cirrhosis.

Conclusions

Treg/Th17 imbalance is involved in the pathogenesis of hepatitis B-associated liver cirrhosis and the Treg/Th17 ratio can be used as a potential marker for predicting decompensated liver cirrhosis.
Literature
1.
go back to reference Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003;23(1):47–58.CrossRef Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003;23(1):47–58.CrossRef
2.
go back to reference Vierling JM. The immunology of hepatitis B. Clin Liver Dis. 2007;11(4):727–59.CrossRef Vierling JM. The immunology of hepatitis B. Clin Liver Dis. 2007;11(4):727–59.CrossRef
3.
go back to reference Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445–89.CrossRef Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445–89.CrossRef
4.
5.
go back to reference Kleinewietfeld M, Hafler DA. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Semin Immunol. 2013;25(4):305–12.CrossRef Kleinewietfeld M, Hafler DA. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Semin Immunol. 2013;25(4):305–12.CrossRef
6.
go back to reference Niu Y, Liu H, Yin D, Yi R, Chen T, Xue H, et al. The balance between intrahepatic IL-17(+) T cells and Foxp3(+) regulatory T cells plays an important role in HBV-related end-stage liver disease. BMC Immunol. 2011;12:47.CrossRef Niu Y, Liu H, Yin D, Yi R, Chen T, Xue H, et al. The balance between intrahepatic IL-17(+) T cells and Foxp3(+) regulatory T cells plays an important role in HBV-related end-stage liver disease. BMC Immunol. 2011;12:47.CrossRef
7.
go back to reference Nan XP, Zhang Y, Yu HT, Sun RL, Peng MJ, Li Y, et al. Inhibition of viral replication downregulates CD4(+)CD25(high) regulatory T cells and programmed death-ligand 1 in chronic hepatitis B. Viral Immunol. 2012;25(1):21–8.CrossRef Nan XP, Zhang Y, Yu HT, Sun RL, Peng MJ, Li Y, et al. Inhibition of viral replication downregulates CD4(+)CD25(high) regulatory T cells and programmed death-ligand 1 in chronic hepatitis B. Viral Immunol. 2012;25(1):21–8.CrossRef
8.
go back to reference Sato M, Suzuki S, Senoo H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct. 2003;28(2):105–12.CrossRef Sato M, Suzuki S, Senoo H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct. 2003;28(2):105–12.CrossRef
9.
go back to reference Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 2011;25(2):195–206.CrossRef Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 2011;25(2):195–206.CrossRef
10.
go back to reference Mannaerts I, Nuytten NR, Rogiers V, Vanderkerken K, van Grunsven LA, Geerts A. Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo. Hepatology. 2010;51(2):603–14.CrossRef Mannaerts I, Nuytten NR, Rogiers V, Vanderkerken K, van Grunsven LA, Geerts A. Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo. Hepatology. 2010;51(2):603–14.CrossRef
11.
go back to reference Wells RG. Cellular sources of extracellular matrix in hepatic fibrosis. Clin Liver Dis. 2008;12(4):759–68.CrossRef Wells RG. Cellular sources of extracellular matrix in hepatic fibrosis. Clin Liver Dis. 2008;12(4):759–68.CrossRef
12.
go back to reference Jaffar Z, Ferrini ME, Girtsman TA, Roberts K. Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B-cell recruitment and polymeric IgA and IgM levels in the airways. Eur J Immunol. 2009;39(12):3307–14.CrossRef Jaffar Z, Ferrini ME, Girtsman TA, Roberts K. Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B-cell recruitment and polymeric IgA and IgM levels in the airways. Eur J Immunol. 2009;39(12):3307–14.CrossRef
13.
go back to reference Bilate AM, Lafaille JJ. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol. 2012;30:733–58.CrossRef Bilate AM, Lafaille JJ. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol. 2012;30:733–58.CrossRef
14.
go back to reference Sakaguchi S. Regulatory T cells: history and perspective. Methods Mol Biol. 2011;707:3–17.CrossRef Sakaguchi S. Regulatory T cells: history and perspective. Methods Mol Biol. 2011;707:3–17.CrossRef
15.
go back to reference Claassen MA, de Knegt RJ, Tilanus HW, Janssen HL, Boonstra A. Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. J Hepatol. 2010;52(3):315–21.CrossRef Claassen MA, de Knegt RJ, Tilanus HW, Janssen HL, Boonstra A. Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. J Hepatol. 2010;52(3):315–21.CrossRef
16.
go back to reference Zhang LJ, Zheng WD, Chen YX, Huang YH, Chen ZX, Zhang SJ, et al. Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis. Hepatogastroenterology. 2007;54(79):2092–8.PubMed Zhang LJ, Zheng WD, Chen YX, Huang YH, Chen ZX, Zhang SJ, et al. Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis. Hepatogastroenterology. 2007;54(79):2092–8.PubMed
17.
go back to reference Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32.CrossRef Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32.CrossRef
18.
go back to reference O'Quinn DB, Palmer MT, Lee YK, Weaver CT. Emergence of the Th17 pathway and its role in host defense. Adv Immunol. 2008;99:115–63.CrossRef O'Quinn DB, Palmer MT, Lee YK, Weaver CT. Emergence of the Th17 pathway and its role in host defense. Adv Immunol. 2008;99:115–63.CrossRef
19.
go back to reference Sun HQ, Zhang JY, Zhang H, Zou ZS, Wang FS, Jia JH. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis. J Viral Hepat. 2012;19(6):396–403.CrossRef Sun HQ, Zhang JY, Zhang H, Zou ZS, Wang FS, Jia JH. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis. J Viral Hepat. 2012;19(6):396–403.CrossRef
20.
go back to reference Sparna T, Retey J, Schmich K, Albrecht U, Naumann K, Gretz N, et al. Genome-wide comparison between IL-17 and combined TNF-alpha/IL-17 induced genes in primary murine hepatocytes. BMC Genomics. 2010;11:226.CrossRef Sparna T, Retey J, Schmich K, Albrecht U, Naumann K, Gretz N, et al. Genome-wide comparison between IL-17 and combined TNF-alpha/IL-17 induced genes in primary murine hepatocytes. BMC Genomics. 2010;11:226.CrossRef
21.
go back to reference Tan Z, Qian X, Jiang R, Liu Q, Wang Y, Chen C, et al. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J Immunol. 2013;191(4):1835–44.CrossRef Tan Z, Qian X, Jiang R, Liu Q, Wang Y, Chen C, et al. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J Immunol. 2013;191(4):1835–44.CrossRef
22.
go back to reference Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012;143(3):765–776 e761-763.CrossRef Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012;143(3):765–776 e761-763.CrossRef
23.
go back to reference Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830–5.CrossRef Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830–5.CrossRef
Metadata
Title
Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis
Authors
Yong-Ting Lan
Zhen-li Wang
Peng Tian
Xiao-Na Gong
Yu-Chen Fan
Kai Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2019
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-019-0891-4

Other articles of this Issue 1/2019

Diagnostic Pathology 1/2019 Go to the issue