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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2016; 22(7): 2294-2303
Published online Feb 21, 2016. doi: 10.3748/wjg.v22.i7.2294
Role of Tim-3 in hepatitis B virus infection: An overview
Yuan Liu, Li-Fen Gao, Xiao-Hong Liang, Chun-Hong Ma
Yuan Liu, Li-Fen Gao, Xiao-Hong Liang, Chun-Hong Ma, Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan 250012, Shandong Province, China
Author contributions: Liu Y wrote the paper; Gao LF and Liang XH provided helpful discussion and critical draft editing; Ma CH performed the literature review and analysis, drafting, critical revision and editing of the original manuscript; and final approval of the final manuscript.
Supported by the National Natural Science Fund for Outstanding Youth Fund, No. 81425012; National Nature Science Foundation of China, No. 81100203, No. 81371831 and No. 91129704; and Research Fund for the Doctoral Program of Higher Education of China (RFDP), No. 20110131110034.
Conflict-of-interest statement: The authors of this manuscript declare no conflict of interest.
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: Chun-Hong Ma, PhD, Professor of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, Shandong Province, China. machunhong@sdu.edu.cn
Telephone: +86-531-88382038 Fax: +86-531-88382052
Received: August 2, 2015
Peer-review started: August 3, 2015
First decision: September 9, 2013
Revised: October 8, 2015
Accepted: December 19, 2015
Article in press: December 19, 2015
Published online: February 21, 2016
Abstract

Hepatitis B virus (HBV) infection has received increasing public attention. HBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the above-mentioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of HBV-related liver disease and suggest new therapeutic methods for intervention.

Keywords: Tim-3, Hepatitis B virus, Inflammation, Immunity, Liver disease

Core tip: Here, we discuss the current knowledge of the interaction between hepatitis B virus (HBV) and host immunity, addressing the important role of T cell immunoglobulin domain and mucin domain-3 (Tim-3) in HBV infection. Tim-3 expression on both adaptive and innate immune cells is elevated in HBV infection. Increasing Tim-3 expression inhibits, and blocking Tim-3 expression rescues, the anti-viral immune response, indicating that Tim-3 is a potential target for controlling HBV infection. Finally, we describe remaining unsolved problems in this field and analyze the potential of Tim-3 as a novel drug target in the treatment of HBV-related liver diseases.