Interleukin-17–Producing Cd4+ T Cells Increase With... : Hepatology (original) (raw)

Viral Hepatitis

Interleukin-17–Producing Cd4+ T Cells Increase With Severity of Liver Damage in Patients With Chronic Hepatitis B

Zhang, Ji-Yuan1,*; Zhang, Zheng1,*; Lin, Fang2; Zou, Zheng-Sheng2; Xu, Ruo-Nan1; Jin, Lei1; Fu, Jun-Liang1; Shi, Feng1; Shi, Ming1; Wang, Hui-Fen2,†; Wang, Fu-Sheng1,†

1_Research Center for Biological Therapy, Beijing, China_

2_Department of Infectious Diseases, Beijing 302 Hospital, Beijing, China_

*Address reprint requests to: Research Center for Biological Therapy, Beijing 302 Hospital, 100039, China. Email:[email protected]; fax: 86-010-63879735; and Prof. Hui-Fen Wang ([email protected]).

Received 21 April 2009; Accepted 30 August 2009

Published online 9 September 2009 in Wiley InterScience (www.interscience.wiley.com).

Supported by grants from the National Grand Program on Key Infectious Disease (No. 2009ZX10004-309, No. 2008ZX10002-007, and No. 2008ZX10002-005-6), the National Key Basic Research Program of China (No. 2007CB512805), the Key Program of National Natural Science Foundation of China (No. 30730088), and the National Laboratory of Biomacromolecules, Institute of Biophysics, China Academy of Sciences.

Potential conflict of interest: Nothing to report.

*Address reprint requests to: These authors contributed equally to this work.

Additional Supporting Information may be found in the online version of this article.

Abstract

Interleukin-17 (IL-17)-producing CD4+ T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro , IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients. Conclusion: Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection. (Hepatology 2009.)