IL-21在HBV感染中的作用

李媛; 黄古叶

doi:10.3969/j.issn.1001-5256.2017.12.038

IL-21在HBV感染中的作用

DOI: 10.3969/j.issn.1001-5256.2017.12.038

李媛,
黄古叶

广西中医药大学第一附属医院肝病科

基金项目:

广西高校中青年教师基础能力提升项目(2017KY0309)；

详细信息

中图分类号: R512.62
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- 被引次数: 0
出版历程
- 收稿日期: 2017-06-26
- 出版日期: 2017-12-20

The role of interleukin-21 in hepatitis B virus infection

Li Yuan,
Huang GuYe

Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine

Research funding:

摘要

摘要: IL-21是一种活化的CD4+T淋巴细胞分泌的细胞因子,能够影响各种淋巴细胞的功能。值得注意的是,IL-21介导的细胞和体液免疫应答在决定病毒感染的结局方面起着重要作用。介绍了关于IL-21在HBV感染中起重要作用的研究进展。病毒特异性CD4+T淋巴细胞分泌的IL-21在维持CD8+T淋巴细胞应答和促进B淋巴细胞应答方面起着关键作用,对于有效地控制病毒至关重要。然而,IL-21作为炎症介质也参与乙型肝炎相关肝硬化的发展和肝损伤的加重。因此,认为在HBV感染中IL-21是一种免疫调节细胞因子。免疫治疗策略的目的是在HBV感染中优化IL-21的有益作用,这在未来可能是一个严峻的挑战。
- 肝炎病毒,乙型 /
- 淋巴细胞活化 /
- 白细胞介素21 /
- 综述
Abstract: 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.
- hepatitis B virus /
- lymphocyte activation /
- interleukin-21 /
- review

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参考文献(37)

[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.

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