title: Restoring homeostasis of CD4⁺ T cells in hepatitis-B-virus-related liver fibrosis.
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.
authors.affiliation: Li-Sha Cheng, Yun Liu, Wei Jiang, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Cheng
authors.affiliation: Li-Sha Cheng, Yun Liu, Wei Jiang, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Li-Sha Cheng, Yun Liu, Wei Jiang, Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D008103:Liver Cirrhosis / Q000276:immunology* / Q000821:virology; D008565:Membrane Proteins / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D043885:Receptor, Cannabinoid, CB2 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; C571431:Cnr2 protein, mouse; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007378:Interleukins; D008565:Membrane Proteins; D061026:Programmed Cell Death 1 Receptor; D043885:Receptor, Cannabinoid, CB2
keywords: CD4+ T cells; Chronic hepatitis B; Homeostasis; Liver fibrosis; Pathogenesis; Regulatory T cells; T helper 17 cells; Therapy