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Volume 38 Issue 6
Jun.  2022
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Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(6): 1393-1397

Association of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 5 with regulatory T cell/T helper 17 cell balance in chronic hepatitis B

DOI: 10.3969/j.issn.1001-5256.2022.06.036
  • 1.

    NHC Key Laboratory of Drug Addiction Medicine, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

  • 2.

    School of Public Health, Kunming Medical University, Kunming 650500, China

More Information
  • Corresponding author: YOU Jing, jingyoukm@126.com(ORCID: 0000-0002-5919-5864)
  • Received Date: 2021-09-26
  • Accepted Date: 2021-11-02
  • Published Date: 2022-06-20
    Abstract
  • The immune mechanism of chronic hepatitis B (CHB) persistent infection is closely associated with T cells, and the development of T cells requires the coordination of a variety of cytokines. The proteins of the signal transducer and activator of transcription (STAT) family are mainly involved in the signal transduction of cytokines, and STAT5a/b and STAT3 play an important role in the differentiation and development of regulatory T cells (Treg) and T helper 17 cells (Th17). This article analyzes the association of STAT3 and STAT5 with Treg/Th17 balance in CHB and investigates the chronicity of hepatitis B virus infection and the regulatory mechanism of liver inflammation.

     

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  • [1]
    BURNS GS, THOMPSON AJ. Viral hepatitis B: clinical and epidemiological characteristics[J]. Cold Spring Harb Perspect Med, 2014, 4(12): a024935. DOI: 10.1101/cshperspect.a024935.
    [2]
    DONG Y, LI X, YU Y, et al. JAK/STAT signaling is involved in IL-35-induced inhibition of hepatitis B virus antigen-specific cytotoxic T cell exhaustion in chronic hepatitis B[J]. Life Sci, 2020, 252: 117663. DOI: 10.1016/j.lfs.2020.117663.
    [3]
    LIU B, GAO W, ZHANG L, et al. Th17/Treg imbalance and increased interleukin-21 are associated with liver injury in patients with chronic severe hepatitis B[J]. Int Immunopharmacol, 2017, 46: 48-55. DOI: 10.1016/j.intimp.2017.02.019.
    [4]
    NIU Y, LIU H, YIN D, et al. The balance between intrahepatic IL-17(+) T cells and Foxp3(+) regulatory T cells plays an important role in HBV-related end-stage liver disease[J]. BMC Immunol, 2011, 12: 47. DOI: 10.1186/1471-2172-12-47.
    [5]
    JIA GH, YOU J, LI J, et al. Role of Foxp3/Treg and RORγt/Th17 imbalance in chronic hepatitis B virus infection[J]. World Chin J Digestol, 2019, 27(11): 709-714. DOI: 10.11569/wcjd.v27.i11.709.

    贾冠华, 游晶, 李静, 等. Foxp3/Treg与RORγt/Th17失衡在慢性乙型肝炎病毒感染中的作用[J]. 世界华人消化杂志, 2019, 27(11): 709-714. DOI: 10.11569/wcjd.v27.i11.709.
    [6]
    CAI Y, PAN L, LIN B, et al. Relationship between Treg/Th17 balance and changes in HBeAg among HBeAg-positive chronic hepatitis B patients receiving entecavir therapy[J]. Int J Virol, 2020, 27(5): 407-411. DOI: 10.3760/cma.j.issn.1673-4092.2020.05.013.

    蔡云, 潘良, 林斌, 等. 恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者外周血Treg/Th17平衡与HBeAg的变化[J]. 国际病毒学杂志, 2020, 27(5): 407-411. DOI: 10.3760/cma.j.issn.1673-4092.2020.05.013.
    [7]
    CHEN J, WANG L, FU Y, et al. The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection[J]. Hepatol Int, 2014, 8(1): 55-63. DOI: 10.1007/s12072-013-9464-x.
    [8]
    GAO B, WANG H, LAFDIL F, et al. STAT proteins - key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver[J]. J Hepatol, 2012, 57(2): 430-441. DOI: 10.1016/j.jhep.2012.01.029.
    [9]
    KONG X, HORIGUCHI N, MORI M, et al. Cytokines and STATs in liver fibrosis[J]. Front Physiol, 2012, 3: 69. DOI: 10.3389/fphys.2012.00069.
    [10]
    DING FM, LIAO RM, CHEN YQ, et al. Upregulation of SOCS3 in lung CD4+ T cells in a mouse model of chronic PA lung infection and suppression of Th17-mediated neutrophil recruitment in exogenous SOCS3 transfer in vitro[J]. Mol Med Rep, 2017, 16(1): 778-786. DOI: 10.3892/mmr.2017.6630.
    [11]
    JIANG Y, WANG X, DONG C. Molecular mechanisms of T helper 17 cell differentiation: Emerging roles for transcription cofactors[J]. Adv Immunol, 2019, 144: 121-153. DOI: 10.1016/bs.ai.2019.09.003.
    [12]
    DURANT L, WATFORD WT, RAMOS HL, et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis[J]. Immunity, 2010, 32(5): 605-615. DOI: 10.1016/j.immuni.2010.05.003.
    [13]
    O'SHEA JJ, LAHESMAA R, VAHEDI G, et al. Genomic views of STAT function in CD4+ T helper cell differentiation[J]. Nat Rev Immunol, 2011, 11(4): 239-250. DOI: 10.1038/nri2958.
    [14]
    YANG XO, PANOPOULOS AD, NURIEVA R, et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells[J]. J Biol Chem, 2007, 282(13): 9358-9363. DOI: 10.1074/jbc.C600321200.
    [15]
    LIAO W, SCHONES DE, OH J, et al. Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression[J]. Nat Immunol, 2008, 9(11): 1288-1296. DOI: 10.1038/ni.1656.
    [16]
    ZORN E, NELSON EA, MOHSENI M, et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo[J]. Blood, 2006, 108(5): 1571-1579. DOI: 10.1182/blood-2006-02-004747.
    [17]
    HATZIOANNOU A, BOUMPAS A, PAPADOPOULOU M, et al. Regulatory T cells in autoimmunity and cancer: A duplicitous lifestyle[J]. Front Immunol, 2021, 12: 731947. DOI: 10.3389/fimmu.2021.731947.
    [18]
    SHATROVA AN, MITYUSHOVA EV, VASSILIEVA IO, et al. Time-dependent regulation of IL-2R α-Chain (CD25) expression by TCR signal strength and IL-2-Induced STAT5 signaling in activated human blood T lymphocytes[J]. PLoS One, 2016, 11(12): e0167215. DOI: 10.1371/journal.pone.0167215.
    [19]
    SOEHARSO P, SUMMERS KM, COOKSLEY WG. Allotype distribution of human T cell receptor beta and gamma chain genes in Caucasians, Asians and Australian aborigines: relevance to chronic hepatitis B[J]. Hum Genet, 1992, 89(1): 59-63. DOI: 10.1007/BF00207043.
    [20]
    YAO Z, CUI Y, WATFORD WT, et al. Stat5a/b are essential for normal lymphoid development and differentiation[J]. Proc Natl Acad Sci U S A, 2006, 103(4): 1000-1005. DOI: 10.1073/pnas.0507350103.
    [21]
    LAURENCE A, TATO CM, DAVIDSON TS, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation[J]. Immunity, 2007, 26(3): 371-381. DOI: 10.1016/j.immuni.2007.02.009.
    [22]
    PANDIYAN P, YANG XP, SARAVANAMUTHU SS, et al. The role of IL-15 in activating STAT5 and fine-tuning IL-17A production in CD4 T lymphocytes[J]. J Immunol, 2012, 189(9): 4237-4246. DOI: 10.4049/jimmunol.1201476.
    [23]
    YANG XP, GHORESCHI K, STEWARD-THARP SM, et al. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5[J]. Nat Immunol, 2011, 12(3): 247-254. DOI: 10.1038/ni.1995.
    [24]
    LIU C, XU L, XIA C, et al. Increased proportion of functional subpopulations in circulating regulatory T cells in patients with chronic hepatitis B[J]. Hepatol Res, 2020, 50(4): 439-452. DOI: 10.1111/hepr.13472.
    [25]
    FENG C, CAO LJ, SONG HF, et al. Expression of PD-L1 on CD4+CD25+Foxp3+ regulatory T cells of patients with chronic HBV infection and its correlation with clinical parameters[J]. Viral Immunol, 2015, 28(8): 418-424. DOI: 10.1089/vim.2015.0062.
    [26]
    COLLISON LW, CHATURVEDI V, HENDERSON AL, et al. IL-35-mediated induction of a potent regulatory T cell population[J]. Nat Immunol, 2010, 11(12): 1093-1101. DOI: 10.1038/ni.1952.
    [27]
    PARFIENIUK-KOWERDA A, JAROSZEWICZ J, FLISIAK R. Immune regulation and viral diversity as correlates of natural and treatment induced immune control in persistent hepatitis B virus (HBV) infection[J]. Clin Exp Hepatol, 2015, 1(2): 35-38. DOI: 10.5114/ceh.2015.51805.
    [28]
    YANG L, HU XQ, FU WZ. Correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis B[J]. J Hainan Med Univ, 2017, 23(11): 1478-1480, 1484. DOI: 10.13210/j.cnki.jhmu.20170607.002.

    杨丽, 胡晓勤, 付万智. 外周血Th17细胞表面CCR4、CCR6、CXCR3表达量与慢性乙型肝炎患者病情的相关性[J]. 海南医学院学报, 2017, 23(11): 1478-1480, 1484. DOI: 10.13210/j.cnki.jhmu.20170607.002.
    [29]
    VELDHOEN M, HOCKING RJ, ATKINS CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells[J]. Immunity, 2006, 24(2): 179-189. DOI: 10.1016/j.immuni.2006.01.001.
    [30]
    LIU B, GAO W, ZHANG L, et al. Th17/Treg imbalance and increased interleukin-21 are associated with liver injury in patients with chronic severe hepatitis B[J]. Int Immunopharmacol, 2017, 46: 48-55. DOI: 10.1016/j.intimp.2017.02.019.
    [31]
    KHOURIEH J, RAO G, HABIB T, et al. A deep intronic splice mutation of STAT3 underlies hyper IgE syndrome by negative dominance[J]. Proc Natl Acad Sci U S A, 2019, 116(33): 16463-16472. DOI: 10.1073/pnas.1901409116.
    [32]
    TANG Y, TAN SA, IQBAL A, et al. STAT3 genotypic variant rs744166 and increased tyrosine phosphorylation of STAT3 in IL-23 responsive innate lymphoid cells during pathogenesis of crohn's disease[J]. J Immunol Res, 2019, 2019: 9406146. DOI: 10.1155/2019/9406146.
    [33]
    DAVIDSON SI, LIU Y, DANOY PA, et al. Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese[J]. Ann Rheum Dis, 2011, 70(2): 289-292. DOI: 10.1136/ard.2010.133322.
    [34]
    FOSHAY KM, GALLICANO GI. miR-17 family miRNAs are expressed during early mammalian development and regulate stem cell differentiation[J]. Dev Biol, 2009, 326(2): 431-443. DOI: 10.1016/j.ydbio.2008.11.016.
    [35]
    FAN JJ, CHANG CF, WANG H. Association of single-nucleotide polymorphisms of STAT3and STAT4 with hepatocellular carcinoma[J]. J Pract Med, 2018, 34(21): 3593-3597, 3602. DOI: 10.3969/j.issn.1006-5725.2018.21.025.

    范敬静, 常彩芳, 王浩. STAT3和STAT4基因单核苷酸多态性与肝细胞癌的相关性[J]. 实用医学杂志, 2018, 34(21): 3593-3597, 3602. DOI: 10.3969/j.issn.1006-5725.2018.21.025.
    [36]
    SHI H, HE H, OJHA SC, et al. Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis[J]. Biosci Rep, 2019, 39(6): BSR20190783. DOI: 10.1042/BSR20190783.
    [37]
    XIE J, ZHANG Y, ZHANG Q, et al. Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma[J]. Hepatology, 2013, 57(6): 2369-2377. DOI: 10.1002/hep.26303.
    [38]
    YIN JP, YUE ZC, ZHUO SY. STAT3: A key molecule in the progression of liver cancer mediated by chronic inflammation[J]. J Clin Hepatol, 2020, 36(4): 948-952. DOI: 10.3969/j.issn.1001-5256.2020.04.054.

    音金萍, 岳紫晨, 卓少元. STAT3: 慢性炎症介导肝癌进程的关键分子[J]. 临床肝胆病杂志, 2020, 36(4): 948-952. DOI: 10.3969/j.issn.1001-5256.2020.04.054.
    [39]
    FATEMIPOUR M, ARABZADEH S, MOLAEI H, et al. Evaluation of STAT3 rs1053004 single nucleotide polymorphism in patients with chronic hepatitis B and hepatocellular carcinoma[J]. Cell Mol Biol (Noisy-le-grand), 2017, 63(12): 45-50. DOI: 10.14715/cmb/2017.63.12.11.
    [40]
    LI M, LI F, LI N, et al. Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population[J]. BMC Med Genet, 2018, 19(1): 52. DOI: 10.1186/s12881-018-0569-x.
    [41]
    ZHAO X, JIANG K, LIANG B, et al. STAT4 gene polymorphism and risk of chronic hepatitis B-induced hepatocellular carcinoma[J]. Cell Biochem Biophys, 2015, 71(1): 353-357. DOI: 10.1007/s12013-014-0205-0.
    [42]
    ZHANG L, XU K, LIU C, et al. Meta-analysis reveals an association between signal transducer and activator of transcription-4 polymorphism and hepatocellular carcinoma risk[J]. Hepatol Res, 2017, 47(4): 303-311. DOI: 10.1111/hepr.12733.
    [43]
    YANG Y, ZHENG B, HAN Q, et al. Targeting blockage of STAT3 inhibits hepatitis B virus-related hepatocellular carcinoma[J]. Cancer Biol Ther, 2016, 17(4): 449-456. DOI: 10.1080/15384047.2016.1156257.
    [44]
    WARIS G, HUH KW, SIDDIQUI A. Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress[J]. Mol Cell Biol, 2001, 21(22): 7721-7730. DOI: 10.1128/MCB.21.22.7721-7730.2001.
    [45]
    FANG Z, LI J, YU X, et al. Polarization of monocytic myeloid-derived suppressor cells by hepatitis b surface antigen is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B virus infection[J]. J Immunol, 2015, 195(10): 4873-4883. DOI: 10.4049/jimmunol.1501362.
    [46]
    MA Y, LI B, LI Y, et al. Expressions of HBx and ANGPTL4 in liver cancer tissues and their relationships with clinical pathology and prognosis[J]. Med & Pharm J Chin PLA, 2021, 256(10): 41-45. DOI: 10.3969/j.issn.2095-140X.2021.10.010.

    马艳, 黎蓓, 李盈, 等. 肝癌组织HBx和ANGPTL4表达及与临床病理、预后的关系[J]. 解放军医药杂志, 2021, 256(10): 41-45. DOI: 10.3969/j.issn.2095-140X.2021.10.010.
    [47]
    GAN CJ, LI WF, LI CN, et al. EGF receptor inhibitors comprehensively suppress hepatitis B virus by downregulation of STAT3 phosphorylation[J]. Biochem Biophys Rep, 2020, 22: 100763. DOI: 10.1016/j.bbrep.2020.100763.
    [48]
    STIFTER SA, FENG CG. Interfering with immunity: detrimental role of type Ⅰ IFNs during infection[J]. J Immunol, 2015, 194(6): 2455-2465. DOI: 10.4049/jimmunol.1402794.
    [49]
    IVASHKIV LB, DONLIN LT. Regulation of type Ⅰ interferon responses[J]. Nat Rev Immunol, 2014, 14(1): 36-49. DOI: 10.1038/nri3581.
    [50]
    PAN J, ZHANG M, YAO TT, et al. Efficacy and influencing factors of interferon in the treatment of chronic hepatitis B aged 1~6 years[J]. Int J Virol, 2020, 3(3): 214-218. DOI: 10.3760/cma.j.issn.1673-4092.2020.03.009.

    潘静, 张敏, 姚甜甜, 等. 干扰素治疗1~6岁慢性乙型肝炎的疗效及影响因素[J]. 国际病毒学杂志, 2020, 3(3): 214-218. DOI: 10.3760/cma.j.issn.1673-4092.2020.03.009.
    [51]
    SADLER AJ, WILLIAMS BR. Interferon-inducible antiviral effectors[J]. Nat Rev Immunol, 2008, 8(7): 559-568. DOI: 10.1038/nri2314.
    [52]
    WANG WB, LEVY DE, LEE CK. STAT3 negatively regulates type Ⅰ IFN-mediated antiviral response[J]. J Immunol, 2011, 187(5): 2578-2585. DOI: 10.4049/jimmunol.1004128.
    [53]
    PENG YJ, YOU J, LI J, et al. Role of the JAK/STAT/SOCS signaling pathway in hepatitis B virus-related liver diseases[J]. J Clin Hepatol, 2021, 37(6): 1435-1439. DOI: 10.3969/j.issn.1001-5256.2021.06.045.

    彭玉娟, 游晶, 李静, 等. JAK/STAT/SOCS信号通路在HBV相关肝脏疾病中的作用[J]. 临床肝胆病杂志, 2021, 37(6): 1435-1439. DOI: 10.3969/j.issn.1001-5256.2021.06.045.
    [54]
    TAI WT, CHENG AL, SHIAU CW, et al. Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma[J]. J Hepatol, 2011, 55(5): 1041-1048. DOI: 10.1016/j.jhep.2011.01.047.
    [55]
    BLECHACZ BR, SMOOT RL, BRONK SF, et al. Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2[J]. Hepatology, 2009, 50(6): 1861-1870. DOI: 10.1002/hep.23214.
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