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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2015; 21(38): 10721-10731
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10721
Restoring homeostasis of CD4+ T cells in hepatitis-B-virus-related liver fibrosis
Li-Sha Cheng, Yun Liu, Wei Jiang
Li-Sha Cheng, Yun Liu, Wei Jiang, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Author contributions: Cheng LS and Liu Y acquired data; Cheng LS drafted the manuscript; Jiang W critically revised the manuscript for important intellectual content.
Supported by The National Natural Science Foundation of China, No. 81070341 and No. 81270517.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest in this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wei Jiang, Professor, Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. jiang.wei@zs-hospital.sh.cn
Telephone: +86-21-64041990-2424 Fax: +86-21-64432583
Received: April 26, 2015
Peer-review started: April 28, 2015
First decision: June 2, 2015
Revised: June 19, 2015
Accepted: September 2, 2015
Article in press: September 2, 2015
Published online: October 14, 2015
Processing time: 171 Days and 11.9 Hours
Abstract

Immune-mediated liver injury is widely seen during hepatitis B virus (HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis (HBVLF), occurring as a result of HBV-induced chronic hepatitis, is a reversible, intermediate stage of chronic hepatitis B (CHB) and liver cirrhosis. Therefore, defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently, the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms, in this review, we systematically retrospect the impacts of different CD4+ T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T (Treg) and T helper 17 (Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin (IL)-17, IL-22, IL-21, IL-23, IL-10, IL-35 and IL-33, as well as surface molecules such as programmed cell death protein 1, cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.

Keywords: Homeostasis; Regulatory T cells; T helper 17 cells; CD4+ T cells; Liver fibrosis; Chronic hepatitis B; Pathogenesis; Therapy

Core tip: Hepatitis B virus (HBV)-related liver fibrosis (HBVLF) is a reversible, intermediate stage of chronic hepatitis B and liver cirrhosis. The homeostasis of CD4+ T cells, especially the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells is pivotal in HBVLF. Therefore, uncovering the underlying mechanisms of CD4+ T cell homeostasis regulating HBVLF may help achieve better clinical outcomes. We discuss Treg and Th17 cell-related cytokines and surface molecules that may be targeted therapeutically to alter CD4+ T-cell homeostasis in chronic HBV infection.