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辅助性T淋巴细胞17/调节性T淋巴细胞比值失衡在HBV相关肝脏疾病进展中的作用

唐光俊 游晶 刘怀鄂 彭玉娟

引用本文:
Citation:

辅助性T淋巴细胞17/调节性T淋巴细胞比值失衡在HBV相关肝脏疾病进展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.02.035
基金项目: 

国家自然科学基金 (81760111);

国家自然科学基金 (81760617);

云南省应用基础研究项目 (2017FE468〔-033〕)

作者贡献声明:唐光俊负责文献阅读,撰写论文;刘怀鄂、彭玉娟负责提供意见并修改;游晶负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    作者简介:

    唐光俊(1995—),男,主要从事肝病临床基础研究

    通信作者:

    游晶,jingyoukm@126.com

  • 中图分类号: R512.62

Role of T helper 17 cell/regulatory T cell imbalance in the progression of HBV-related liver diseases

  • 摘要: 慢性乙型肝炎患者肝脏损害多发生在免疫介导作用下,考虑病毒感染和免疫反应的相互作用是疾病病情进展的重要原因。慢性乙型肝炎可发展至肝纤维化、肝硬化甚至肝细胞癌。回顾了辅助性T淋巴细胞17(Th17)与调节性T淋巴细胞(Treg)的发现起源,叙述了二者自身特性,同时阐述了在维持免疫系统稳定过程中二者所起的作用及作用机制;详细分析了细胞失衡在慢性乙型肝炎、肝纤维化、肝硬化、肝细胞癌等各个阶段中的作用,指出Th17/Treg失衡会促使HBV相关肝脏疾病病情加重。

     

  • [1] HARRINGTON LE, HATTON RD, MANGAN PR, et al. Interleukin 17 producing CD4+ effector T cells develop via a lineage distinct fromthe T helper type 1 and 2 lineages[J]. Nat Immunol, 2005, 6 (11): 1123-1132. DOI: 10.1038/ni1254
    [2] HIRAHARA K, GHORESCHI K, LAURENCE A, et al. Signal transduction pathways and transcriptional regulation in Th17 cell differentiation[J]. Cytokine Growth Factor Rev, 2010, 21(6): 425-434. DOI: 10.1016/j.cytogfr.2010.10.006
    [3] YANG XO, PAPPU BP, NURIEVA R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma[J]. Immunity, 2008, 28(1): 29-39. DOI: 10.1016/j.immuni.2007.11.016
    [4] KIM HY, JHUN JY, CHO ML, et al. Interleukin-6 upregulates Th17 response via mTOR/STAT3 pathway in acute-on-chronic hepatitis B liver failure[J]. J Gastroenterol, 2014, 49(8): 1264-1273. DOI: 10.1007/s00535-013-0891-1
    [5] CHEN J, LIAO MY, GAO XL, et al. IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1[J]. Cell Physiol Biochem, 2013, 32(5): 1265-1274. DOI: 10.1159/000354525
    [6] SAKAGUCHI S, SAKAGUCHI N, ASANO M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. J Immunol, 1995, 155(3): 1151-1164.
    [7] SAKAGUCHI S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self[J]. Nat Immunol, 2005, 6(4): 345-352. DOI: 10.1038/ni1178
    [8] LIU J, WANG CL, GU X, et al. Correlation relationship between imbalance of Th17/Treg cells and hepatitis B virus infection liver disease[J]. J North Sichuan Med Coll, 2017, 32(3): 479-482. (in Chinese) DOI: 10.3969/j.issn.1005-3697.2017.03.045

    刘娇, 王川林, 古雪, 等. Thl7/Treg细胞失衡与乙肝病毒感染相关性肝病的关系[J]. 川北医学院学报, 2017, 32(3): 479-482. DOI: 10.3969/j.issn.1005-3697.2017.03.045
    [9] NACKA-ALEKSIC' M, STOJANOVIC' M, PILIPOVIC' I, et al. Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization[J]. PLoS One, 2018, 13(8): e0201848. DOI: 10.1371/journal.pone.0201848
    [10] ZIEGLER SF, BUCKNER JH. FOXP3 and the regulation of Treg/Th17 differentiation[J]. Microbes Infect, 2009, 11(5): 594-598. DOI: 10.1016/j.micinf.2009.04.002
    [11] LI P, SPOLSKI R, LIAO W, et al. Complex interactions of transcription factors in mediating cytokine biology in T cells[J]. Immunol Rev, 2014, 261(1): 141-156. DOI: 10.1111/imr.12199
    [12] LIM HW, LEE J, HILLSAMER P, et al. Human Th17 cells share major trafficking receptors with both polarized effector T cells and FOXP3+ regulatory T cells[J]. J Immunol, 2008, 180(1): 122-129. DOI: 10.4049/jimmunol.180.1.122
    [13] SIERRO S, ROMERO P, SPEISER DE. The CD4-like molecule LAG-3, biology and therapeutic applications[J]. Expert Opin Ther Targets, 2011, 15(1): 91-101. DOI: 10.1517/14712598.2011.540563
    [14] YIN J, XU DH, FENG H. The role of Th17/Treg cells in pathogenesis and clinical outcome of chronic hepatitis B[J]. J Prac Hepatol, 2011, 14(5): 389-392. (in Chinese) DOI: 10.3969/j.issn.1672-5069.2011.05.035

    殷杰, 徐栋花, 冯灏. Th17/Treg细胞在慢性乙型肝炎发病机制及临床转归中的作用[J]. 实用肝脏病杂志, 2011, 14(5): 389-392. DOI: 10.3969/j.issn.1672-5069.2011.05.035
    [15] PAQUISSI FC. Immunity and fibrogenesis: The role of Th17/IL-17 axis in HBV and HCV-induced chronic hepatitis and progression to cirrhosis[J]. Front Immunol, 2017, 8: 1195. DOI: 10.3389/fimmu.2017.01195
    [16] LI Z, NIE L, CHEN L, et al. Rapamycin relieves inflammation of experimental autoimmune encephalomyelitis by altering the balance of Treg/Th17 in a mouse model[J]. Neurosci Lett, 2019, 705: 39-45. DOI: 10.1016/j.neulet.2019.04.035
    [17] LU H, DAI X, LI X, et al. Gal-1 regulates dendritic cells-induced Treg/Th17 balance though NF-κB/RelB-IL-27 pathway[J]. Ann Transl Med, 2019, 7(22): 628. DOI: 10.21037/atm.2019.11.02
    [18] MURPHY KM, STOCKINGER B. Effector T cell plasticity: Flexibility in the face of changing circumstances[J]. Nat Immunol, 2010, 11(8): 674-680. DOI: 10.1038/ni.1899
    [19] IMBRATTA C, LEBLOND MM, BOUZOURÈNE H, et al. Maf deficiency in T cells dysregulates Treg - TH17 balance leading to spontaneous colitis[J]. Sci Rep, 2019, 9(1): 6135. DOI: 10.1038/s41598-019-42486-2
    [20] WU W, LI J, CHEN F, et al. Circulating Th17 cells frequency is associated with the disease progression in HBV infected patients[J]. J Gastroenterol Hepatol, 2010, 25(4): 750-757. DOI: 10.1111/j.1440-1746.2009.06154.x
    [21] ZHANG H, JIANG Z, ZHANG L. Dual effect of T helper cell 17 (Th17) and regulatory T cell (Treg) in liver pathological process: From occurrence to end stage of disease[J]. Int Immunopharmacol, 2019, 69: 50-59. DOI: 10.1016/j.intimp.2019.01.005
    [22] GAO Y, ZHANG M, LI J, et al. Circulating FoxP3+ regulatory T and interleukin17-producing Th17 cells actively influence HBV clearance in de novo hepatitis B birus infected patients after orthotopic liver transplantation[J]. PLoS One, 2015, 10(9): e0137881. DOI: 10.1371/journal.pone.0137881
    [23] YI H, ZHANG Y, YANG X, et al. Hepatitis B core antigen impairs the polarization while promoting the production of inflammatory cytokines of M2 macrophages via the TLR2 pathway[J]. Front Immunol, 2020, 11: 535. DOI: 10.3389/fimmu.2020.00535
    [24] SUN XF, GU L, DENG WS, et al. Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice[J]. World J Gastroenterol, 2014, 20(8): 2062-2070. DOI: 10.3748/wjg.v20.i8.2062
    [25] LIU HE, YOU J, HONG M, et al. Study on the role of the balance Th17/Treg in the development of hepatitis B virus-related liver fibrosis[J]. Chin Gen Pract, 2016, 19(18): 2126-2129. (in Chinese) DOI: 10.3969/j.issn.1007-9572.2016.18.004

    刘怀鄂, 游晶, 洪敏, 等. 辅助性T淋巴细胞17/调节性T淋巴细胞平衡在乙型肝炎病毒感染相关肝纤维化进展过程中的作用研究[J]. 中国全科医学, 2016, 19(18): 2126-2129. DOI: 10.3969/j.issn.1007-9572.2016.18.004
    [26] MENG F, WANG K, AOYAMA T, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice[J]. Gastroenterology, 2012, 143(3): 765-776.e3. DOI: 10.1053/j.gastro.2012.05.049
    [27] FABRE T, KARED H, FRIEDMAN SL, et al. IL-17A enhances the expression of profibrotic genes through upregulation of the TGFβ receptor on hepatic stellate cells in a JNK-dependent manner[J]. J Immunol, 2014, 193(8): 3925-3933. DOI: 10.4049/jimmunol.1400861
    [28] ROBERT S, GICQUEL T, BODIN A, et al. Characterization of the MMP/TIMP imbalance and collagen production induced by IL-1β or TNF-α release from human hepatic stellate cells[J]. PLoS One, 2016, 11(4): e0153118. DOI: 10.1371/journal.pone.0153118
    [29] LI K, LIU H, GUO T. Th17/Treg imbalance is an indicator of liver cirrhosis process and a risk factor for HCC occurrence in HBV patients[J]. Clin Res Hepatol Gastroenterol, 2017, 41(4): 399-407. DOI: 10.1016/j.clinre.2016.12.004
    [30] YANG AT, YAN XZ, ZHAO WS, et al. Molecular mechanism of elastin and its regulatory factors on the formation and reversal of liver fibrosis in a mouse model of liver fibrosis[J]. J Clin Hepatol, 2020, 36(7): 1514-1519.(in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.07.014

    杨爱婷, 严旭禛, 赵文姗, 等. 肝纤维化小鼠模型中弹性蛋白及其调控因子在肝纤维化形成和逆转中的分子机制[J]. 临床肝胆病杂志, 2020, 36(7): 1514-1519. DOI: 10.3969/j.issn.1001-5256.2020.07.014
    [31] LAN YT, WANG ZL, TIAN P, et al. Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis[J]. Diagn Pathol, 2019, 14(1): 114. DOI: 10.1186/s13000-019-0891-4
    [32] LIANG C, BU S, FAN X. Suppressive effect of microRNA-29b on hepatic stellate cell activation and its crosstalk with TGF-β1/Smad3[J]. Cell Biochem Funct, 2016, 34(5): 326-333. DOI: 10.1002/cbf.3193
    [33] XU LN, LI Y, PENG JY. microRNA and drug-induced liver injury[J]. Chin J Clin Pharmacol Ther, 2020, 25(7): 803-809. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YLZL202007015.htm

    许丽娜, 李月, 彭金咏. microRNA与药物性肝损伤[J]. 中国临床药理学与治疗学, 2020, 25(7): 803-809. https://www.cnki.com.cn/Article/CJFDTOTAL-YLZL202007015.htm
    [34] JIANG M, GONG X, XIAO XQ, et al. Expression of serum miRNA-122-3p in patients with CHB treated with PEG-interferon-alpha 2b[J]. Int J Virol, 2019, 26(5): 293-298. (in Chinese) DOI: 10.3760/cma.j.issn.1673-4092.2019.05.002

    蒋敏, 龚兴, 肖新强, 等. 血清miRNA-122-3p在聚乙二醇干扰素-α2b治疗CHB患者中表达的研究[J]. 国际病毒学杂志, 2019, 26(5): 293-298. DOI: 10.3760/cma.j.issn.1673-4092.2019.05.002
    [35] WANG YZ, ZHANG W, WANG YH, et al. Repression of liver cirrhosis achieved by inhibitory effect of miR-454 on hepatic stellate cells activation and proliferation via Wnt10a[J]. J Biochem, 2019, 165(4): 361-367. DOI: 10.1093/jb/mvy111
    [36] LITTMAN DR, RUDENSKY AY. Th17 and regulatory T cells in mediating and restraining inflammation[J]. Cell, 2010, 140(6): 845-858. DOI: 10.1016/j.cell.2010.02.021
    [37] LAN YT, FAN XP, FAN YC, et al. Change in the Treg/Th17 cell imbalance in hepatocellular carcinoma patients and its clinical value[J]. Medicine (Baltimore), 2017, 96(32): e7704. DOI: 10.1097/MD.0000000000007704
    [38] LIN ZW, WU LX, XIE Y, et al. The expression levels of transcription factors T-bet, GATA-3, RORγt and FOXP3 in peripheral blood lymphocyte (PBL) of patients with liver cancer and their significance[J]. Int J Med Sci, 2015, 12(1): 7-16. DOI: 10.7150/ijms.8352
    [39] GAO YW, CHEN YX, WANG ZM, et al. Increased expression of cyclooxygenase-2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma[J]. Digestion, 2009, 79(3): 169-176. DOI: 10.1159/000210266
    [40] ZHOU Y, XU X, DING J, et al. Dynamic changes of T-cell subsets and their relation with tumor recurrence after microwave ablation in patients with hepatocellular carcinoma[J]. J Cancer Res Ther, 2018, 14(1): 40-45. DOI: 10.4103/jcrt.JCRT_775_17
    [41] KINOSHITA M, KOBAYASHI S, GOTOH K, et al. Heterogeneity of Treg/Th17 according to cancer progression and modification in biliary tract cancers via self-producing cytokines[J]. Dig Dis Sci, 2020, 65(10): 2937-2948. DOI: 10.1007/s10620-019-06011-9
    [42] CROCE M, RIGO V, FERRINI S. IL-21: A pleiotropic cytokine with potential applications in oncology[J]. J Immunol Res, 2015, 2015: 696578.
    [43] SHAHID A, BHARADWAJ M. The connection between the Th17 cell related cytokines and cancer stem cells in cancer: Novel therapeutic targets[J]. Immunol Lett, 2019, 213: 9-20. DOI: 10.1016/j.imlet.2019.07.001
    [44] van der HEIDE D, WEISKIRCHEN R, BANSAL R. Therapeutic targeting of hepatic macrophages for the treatment of liver diseases[J]. Front Immunol, 2019, 10: 2852. DOI: 10.3389/fimmu.2019.02852
    [45] ZHANG GL, ZHANG T, ZHAO QY, et al. Th17 cells over 5.9% at admission indicate poor prognosis in patients with HBV-related acute-on-chronic liver failure[J]. Medicine (Baltimore), 2018, 97(40): e12656. DOI: 10.1097/MD.0000000000012656
    [46] JEFFERSON B, ALI M, GRANT S, et al. Thrombospondin-1 exacerbates acute liver failure and hepatic encephalopathy pathology in mice by activating transforming growth factor β1[J]. Am J Pathol, 2020, 190(2): 347-357. DOI: 10.1016/j.ajpath.2019.10.003
    [47] HUANG B, CHENG X, WANG H, et al. Mesenchymal stem cells and their secreted molecules predominantly ameliorate fulminant hepatic failure and chronic liver fibrosis in mice respectively[J]. J Transl Med, 2016, 14: 45. DOI: 10.1186/s12967-016-0792-1
    [48] YANG R, GAO H, CHEN L, et al. Effect of peripheral blood-derived mesenchymal stem cells on macrophage polarization and Th17/Treg balance in vitro[J]. Regen Ther, 2020, 14: 275-283. DOI: 10.1016/j.reth.2020.03.008
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  • 收稿日期:  2020-07-21
  • 录用日期:  2020-09-04
  • 出版日期:  2021-02-20
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