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Involvement of Th17 and Th1 Effector Responses in Patients with Hepatitis B

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Abstract

Background

Local production of cytokines within the liver may play a pivotal role in the regulation of pathophysiological processes during inflammation. CD4+ T cells are regarded as the most prolific cytokine producers. The purpose of this study was to quantify intrahepatic expression of Th1, Th2, Th17, and Treg-associated cytokines or transcription factors in patients with acute hepatitis B or chronic hepatitis B (CHB) and to analyze their relative roles in the promotion and regulation of hepatitis B virus (HBV)-associated liver diseases.

Methods

Distribution and expression of IL-17, IFN-γ, IL-4, Foxp3, and other cytokines in liver tissues were detected by immunohistochemistry and real-time quantitative PCR. Patients with hepatitis B were compared with patients with chronic hepatitis C, primary biliary cirrhosis, alcoholic liver cirrhosis, and healthy controls.

Results

The frequencies of intrahepatic IL-17 and IFN-γ-producing cells in patients with HBV-associated liver dysfunction were much higher than that of IL-4 and Foxp3-positive cells. The level of the IL-17/IFN-γ-positive cell ratio of patients with Child–Pugh class C (1.57 ± 0.09) was much higher than that of patients with Child–Pugh class B (1.00 ± 0.02) or A (0.93 ± 0.05). There are more IL-17-producing cells than IFN-γ-producing cells accumulating in the liver with severe hepatocellular damage. Liver IL-17-producing cell infiltration was positively associated with the grade of liver inflammation in CHB and positively correlated to intrahepatic IL-8 expression (r = 0.801, p < 0.01) or neutrophil infiltration (r = 0.917, p < 0.01).

Conclusions

These results suggest that the balance of effector CD4+ Th responses (Th17 and Th1 responses) and regulatory response is an important element of immune regulation. Inappropriate, excessive, and non-specific Th17 and Th1 effector responses may be involved in the pathogenesis of HBV-associated liver inflammation and hepatocellular damage. Th17 response, especially, may exacerbate the inflammatory processes leading to liver failure. IL-17-mediating liver neutrophil recruitment via induction of IL-8 may be one potential mechanism of liver injury in patients with hepatitis B. An improved understanding of the factors that influence the differentiation and function of these cell types in vivo will be of great importance to the future development of immune therapies in HBV-associated liver disease.

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Sponsor and grant acknowledgements

This work was supported by grants from the National Basic Research Program of China (2009CB522403), National Natural Science Foundation of China (No. 30972795), and National Science and Technology Major Project of China (No. 2008ZX10002-22).

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Authors and Affiliations

  1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China

    Yufu Ye, Xiaojun Xie, Jiwei Yu, Lin Zhou, Haiyang Xie, Guoping Jiang, Xiaobo Yu, Wenjin Zhang, Jian Wu & Shusen Zheng

  2. Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China

    Yufu Ye, Xiaojun Xie, Jiwei Yu, Lin Zhou, Haiyang Xie, Guoping Jiang, Xiaobo Yu, Wenjin Zhang, Jian Wu & Shusen Zheng

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  1. Yufu Ye
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Correspondence to Shusen Zheng.

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Ye, Y., Xie, X., Yu, J. et al. Involvement of Th17 and Th1 Effector Responses in Patients with Hepatitis B. J Clin Immunol 30, 546–555 (2010). https://doi.org/10.1007/s10875-010-9416-3

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  • DOI: https://doi.org/10.1007/s10875-010-9416-3

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