中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 12
Dec.  2017
Turn off MathJax
Article Contents

The role of interleukin-21 in hepatitis B virus infection

DOI: 10.3969/j.issn.1001-5256.2017.12.038
Research funding:

 

  • Received Date: 2017-06-26
  • Published Date: 2017-12-20
  • Interleukin-21 ( IL-21) is a cytokine produced by activated CD4+T cells and can affect the function of various lymphocytes. It should be noted that IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article introduces the research advances in the important role of IL-21 in hepatitis B virus ( HBV) infection. IL-21 secreted by virus-specific CD4+T cells plays key roles in sustaining CD8+T lymphocyte response and promoting B-lymphocyte response, which is vital for effective viral control. However, as an inflammatory mediator, IL-21 is also involved in the development of hepatitis B-related liver cirrhosis and aggravation of liver injury. Therefore, IL-21 is considered as an immunoregulatory cytokine in HBV infection. Immunotherapeutic strategies aim at optimizing the beneficial effects of IL-21 in HBV infection, which may be a serious challenge in the future.

     

  • loading
  • [1]PARRISH-NOVAK J, DILLON SR, NELSON A, et al.Interleukin 21 and its receptor are involved in NK cellexpansion and regulation of lymphocyte function[J].Nature, 2000, 408 (6808) :57-63.
    [2]COQUET JM, KYPARISSOUDIS K, PELLICCI DG, et al.IL-21isproduced by NKT cells and modulates NKT cell activationand cytokine production[J].J Immunol, 2007, 178 (5) :2827-2834.
    [3]SPOLSKI R, LEONARD WJ.Interleukin-21:basic biology and implications for cancer and autoimmunity[J].Annu Rev Immunol, 2008, 26:57-79.
    [4]MONTELEONE G, PALLONE F, MACDONALD TT.Interleukin-21:a critical regulator of the balance between effector and regulatory T-cellresponses[J].Trends Immunol, 2008, 29 (6) :290-294.
    [5]CHEN W, YANG J, LIN D, et al.Optimization of clinical-grade human NK cell culture system with the combination of IL-15 and IL-21 cytokines[J].Chin J Med Offic, 2017, 45 (1) :64-68. (in Chinese) 陈伟, 杨冀, 蔺迪, 等.IL-15与IL-21细胞因子组合优化临床级人NK细胞培养体系[J].临床军医杂志, 2017, 45 (1) :64-68.
    [6]RAN F, KE JW.Research advances in immunoregulatory effect of interleukin-21 in viral infectious disease[J].Exp Lab Med, 2016, 34 (3) :318-321. (in Chinese) 冉飞, 柯江维.IL-21在病毒感染性疾病中的免疫调节效应的研究进展[J].实验与检验医学, 2016, 34 (3) :318-321.
    [7]ZENG R, SPOLSKI R, CASAS E, et al.The molecular basis of IL-21-mediated proliferation[J].Blood, 2007, 109 (10) :4135-4142.
    [8]PUBLICOVER J, GOODSELL A, NISHIMURA S, et al.IL-21 is pivotal in determining age-dependenteffectiveness of immune responses in a mouse model of humanhepatitis B[J].J Clin Invest, 2011, 121 (3) :1154-1162.
    [9]PUBLICOVER J, GAGGAR A, NISHIMURA S, et al.Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B[J].J Clin Invest, 2013, 123 (9) :3728-3739.
    [10]SHIN H, WHERRY EJ.CD8 T cell dysfunction during chronic viral infection[J].Curr Opin Immunol, 2007, 19 (4) :408-415.
    [11]ELSAESSER H, SAUER K, BROOKS DG.IL-21 is required to control chronic viral infection[J].Science, 2009, 324 (5934) :1569-1572.
    [12]MA SW, HUANG X, LI YY, et al.High serum IL-21 levels after 12weeks of antiviral therapy predict HBe Ag seroconversion in chronic hepatitis B[J].J Hepatol, 2012, 56 (4) :775-781.
    [13]DONG J, YANG XF, SHEN HJ, et al.Regulatory effect of gamma-chain cytokines on expression of TIM-3 on CD8+T cells in patients with chronic hepatitis B[J].J Clin Hepatol, 2015, 31 (2) :205-208. (in Chinese) 董杰, 杨晓飞, 申焕君, 等.γ链细胞因子对慢性乙型肝炎患者CD8+T细胞上TIM-3表达的调节[J].临床肝胆病杂志, 2015, 31 (2) :205-208.
    [14]LI Y, MAS, TANG L, et al.Circulating chemokine (C-X-C Motif) receptor 5+CD4+T cells benefit hepatitis B e antigen seroconversion through IL-21 in patients with chronic hepatitis B virus infection[J].Hepatology, 2013, 58 (4) :1277-1286.
    [15]LI L, LIU M, CHENG LW, et al.HBc Ag-specific IL-21-producing CD4+T cells are associated with relative viral control in patients with chronic hepatitis B[J].Scand J Immunol, 2013, 78 (5) :439-446.
    [16]LI J, REN W, MA W, et al.Interleukin-21 responses in patients with chronic hepatitis B[J].J Interferon Cytokine Res, 2015, 35 (2) :134-142.
    [17]REN G, ESSER S, JOCHUM C, et al.Interleukin 21 augments the hepatitis B virus-specific CD8+T-cell response in vitro in patients coinfected with HIV-1[J].AIDS, 2012, 26 (17) :2145-2153.
    [18]CROTTY S.Follicular helper CD4 T cells (TFH) [J].Annu Rev Immunol, 2011, 29:621-663.
    [19]WUENSCH SA, PIERCE RH, CRISPE IN.Local intrahepatic CD8+T cell activation by a non-self-antigen results in full functional differentiation[J].J Immunol, 2006, 177 (3) :1689-1697.
    [20]GRETER M, HOFMANN J, BECHER B.Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity[J].PLo S Biol, 2009, 7 (5) :e1000109.
    [21]CRISPE IN.The liver as a lymphoid organ[J].Annu Rev Immunol, 2009, 27:147-163.
    [22]THOMSON AW, KNOLLE PA.Antigen-presenting cell function in the tolerogenic liver environment[J].Nat Rev Immunol, 2010, 10 (11) :753-766.
    [23]RASHEED MA, LATNER DR, AUBERT RD, et al.Interleukin-21is a critical cytokine for the generation of virusspecific long-lived plasma cells[J].J Virol, 2013, 87 (13) :7737-7746.
    [24]LAU GK, WANG FS.Uncover the immune biomarkers underlying hepatitis B e antigen (HBe Ag) seroconversion:a need for more translational study[J].J Hepatol, 2012, 56 (4) :753-755.
    [25]GIARDA P, AVIHINGSANON A, SASADEUSZ J, et al.CXCL-10, interleukin-12 and interleukin-21 are not immunological predictors of HBe Ag seroconversion in HIV-1-HBV coinfection following HBV-active antiretroviral therapy[J].Antivir Ther, 2014, 19 (4) :429-433.
    [26]COOKSLEY H, CHOKSHI S, MAAYAN Y, et al.Hepatitis B virus e antigen loss during adefovir dipivoxil therapy is associated with enhanced virus-specific CD4+T-cell reactivity[J].Antimicrob Agents Chemother, 2008, 52 (1) :312-320.
    [27]SIMPSON N, GATENBY PA, WILSON A, et al.Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus[J].Arthritis Rheum, 2010, 62 (1) :234-244.
    [28]LINTERMAN MA, VINUESA CG.Signals that influence T follicular helper cell differentiation and function[J].Semin Immunopathol, 2010, 32 (2) :183-196.
    [29]MORITA R, SCHMITT N, BENTEBIBEL SE, et al.Human blood CXCR5+CD4+T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion[J].Immunity, 2011, 34 (1) :108-121.
    [30]CHEVALIER N, JARROSSAY D, HO E, et al.CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses[J].J Immunol, 2011, 186 (10) :5556-5568.
    [31]ZHANG JY, ZHANG Z, LIN F, et al.Interleukin-17-producing CD4+T cells increase with severity of liver damage in patients with chronic hepatitis B[J].Hepatology, 2010, 51 (1) :81-91.
    [32]HU X, MA S, HUANG X, et al.Interleukin-21 is upregulated in hepatitis B-related acute-on-chronic liver failure and associated with severity of liver disease[J].J Viral Hepat, 2011, 18 (7) :458-467.
    [33] PAN XY, CHEN XJ, YAN ZQ, et al.Correlation among HBs Ag and HBV DNA levels with liver fibrosis in patients with hepatitis B[J].Inter J Viro, 2016, 23 (1) :50-52. (in Chinese) 韩晓颖, 陈秀记, 闫泽强, 等.血清HBs Ag与HBV DNA水平与乙肝患者肝纤维化程度的相关性分析[J].国际病毒学杂志, 2016, 23 (1) :50-52.
    [34]PAN Q, YU Y, TANG Z, et al.Increased levels of IL-21 responses are associated with the severity of liver injury in patients with chronic active hepatitis B[J].J Viral Hepat, 2014, 21 (9) :e78-e88.
    [35]SUN HQ, ZHANG JY, ZHANG H, et al.Increased Th17 cells contribute to disease progression in patients with HBV associated liver cirrhosis[J].J Viral Hepat, 2012, 19 (6) :396-403.
    [36]PESCE J, KAVIRATNE M, RAMALINGAM TR, et al.The IL-21receptor augments Th2 effector function and alternative macrophage activation[J].J Clin Invest, 2006, 116 (7) :2044-2055.
    [37]FENG G, ZHANG JY, ZENG QL, et al.Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells[J].Hepatol Res, 2014, 44 (10) :e198-e205.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (1748) PDF downloads(361) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return