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Volume 40 Issue 6
Jun.  2024
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Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(6): 1275-1280

Role of T-cell immunoglobulin and mucin domain-containing molecule 3 in the development and progression of liver diseases

DOI: 10.12449/JCH240632

  • Department of Gastroenterology，The Second Affiliated Hospital of Kunming Medical University，Kunming 650101，China

Research funding:

National Natural Science Foundation of China (82360108);

Yunnan Medical Leading Talent Project (L-2019013);

Yunnan Ten Thousand Talents Project (YNWR-MY-2018-028);

China United Liver Health Promotion Center - Special Fund for Hepatitis E Prevention and Treatment (CLH2023-F-HEV-08);

Yunnan Provincial Science and Technology Talent and Platform Program (Academician Expert Workstation 202305AF150065);

Clinical Research Project of the Second Affiliated Hospital of Kunming Medical University (2020ynlc010);

Clinical Research Project of the Second Affiliated Hospital of Kunming Medical University (ynIIT2021017)

More Information
  • Corresponding author: TANG Yingmei， tangyingmei_med@kmmu.edu.cn （ORICID： 0000-0002-0731-4198）
  • Received Date: 2023-09-06
  • Accepted Date: 2023-10-10
  • Published Date: 2024-06-25
    Abstract
  • T-cell immunoglobulin and mucin domain-containing molecule-3 （Tim-3） is a member of the Tim family and has been a research hotspot in recent years. As a negative regulatory factor， Tim-3 exerts different effects by binding to different ligands. Tim-3 is expressed in various types of immune cells， such as natural killer cells， dendritic cells， and monocytes， and Tim-3 has a regulatory effect on the functions of these immune cells. In recent years， a large number of studies have shown that Tim-3 is closely associated with the development and progression of liver diseases. This article reviews the studies on the role and mechanism of Tim-3 in different liver diseases and cells in recent years， in order to provide richer perspectives and ideas for the clinical diagnosis and treatment of liver diseases.

     

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  • [1]
    CHENG L, RUAN ZH. Tim-3 and Tim-4 as the potential targets for antitumor therapy[J]. Hum Vaccin Immunother, 2015, 11( 10): 2458- 2462. DOI: 10.1080/21645515.2015.1056953.
    [2]
    KANDEL S, ADHIKARY P, LI GF, et al. The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy[J]. Cancer Lett, 2021, 510: 67- 78. DOI: 10.1016/j.canlet.2021.04.011.
    [3]
    SOLINAS C, de SILVA P, BRON D, et al. Significance of TIM3 expression in cancer: From biology to the clinic[J]. Semin Oncol, 2019, 46( 4-5): 372- 379. DOI: 10.1053/j.seminoncol.2019.08.005.
    [4]
    WU SS, DU XF, LOU GH, et al. Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection[J]. BMC Infect Dis, 2022, 22( 1): 842. DOI: 10.1186/s12879-022-07841-1.
    [5]
    CLAYTON KL, DOUGLAS-VAIL MB, NUR-UR RAHMAN AK, et al. Soluble T cell immunoglobulin mucin domain 3 is shed from CD8+ T cells by the sheddase ADAM10, is increased in plasma during untreated HIV infection, and correlates with HIV disease progression[J]. J Virol, 2015, 89( 7): 3723- 3736. DOI: 10.1128/JVI.00006-15.
    [6]
    LAKE CM, VOSS K, BAUMAN BM, et al. TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8+ T cells in conjunction with CEACAM1[J]. Cell Death Dis, 2021, 12( 4): 400. DOI: 10.1038/s41419-021-03689-6.
    [7]
    VISHAL K, VIKAS D, PATIL AM, et al. CEACAM1 promotes CD8+T cell responses and improves control of a chronic viral infection[J]. Nature Communications, 2018, 9( 1): 2561. DOI: 10.1038/s41467-018-04832-2.
    [8]
    SORDI R, ÂC BET, DELLA JUSTINA AM, et al. The apoptosis clearance signal phosphatidylserine inhibits leukocyte migration and promotes inflammation resolution in vivo[J]. Eur J Pharmacol, 2020, 877: 173095. DOI: 10.1016/j.ejphar.2020.173095.
    [9]
    KANE LP. Regulation of Tim-3 function by binding to phosphatidylserine[J]. Biochem J, 2021, 478( 22): 3999- 4004. DOI: 10.1042/BCJ20210652.
    [10]
    WANG JY, LI C, FU JJ, et al. Tim-3 regulates inflammatory cytokine expression and Th17 cell response induced by monocytes from patients with chronic hepatitis B[J]. Scand J Immunol, 2019, 89( 5): e12755. DOI: 10.1111/sji.12755.
    [11]
    DAI SY, NAKAGAWA R, ITOH A, et al. Galectin-9 induces maturation of human monocyte-derived dendritic cells[J]. J Immunol, 2005, 175( 5): 2974- 2981. DOI: 10.4049/jimmunol.175.5.2974.
    [12]
    YU LH, LIU XL, WANG XH, et al. TIGIT+ TIM-3+ NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus-related hepatocellular carcinoma[J]. Oncoimmunology, 2021, 10( 1): 1942673. DOI: 10.1080/2162402X.2021.1942673.
    [13]
    LI F, FAN XD, WANG XY, et al. Genetic association and interaction of PD1 and TIM3 polymorphisms in susceptibility of chronic hepatitis B virus infection and hepatocarcinogenesis[J]. Discov Med, 2019, 27( 147): 79- 92.
    [14]
    MOHAMMADIZAD H, SHAHBAZI M, HASANJANI ROUSHAN MR, et al. TIM-3 as a marker of exhaustion in CD8+ T cells of active chronic hepatitis B patients[J]. Microb Pathog, 2019, 128: 323- 328. DOI: 10.1016/j.micpath.2019.01.026.
    [15]
    HOFMANN M, TAUBER C, HENSEL N, et al. CD8+ T cell responses during HCV infection and HCC[J]. J Clin Med, 2021, 10( 5): 991. DOI: 10.3390/jcm10050991.
    [16]
    LEE HM, BANINI BA. Updates on Chronic HBV: current challenges and future goals[J]. Curr Treat Options Gastroenterol, 2019, 17( 2): 271- 291. DOI: 10.1007/s11938-019-00236-3.
    [17]
    VIMALI J, YONG YK, MURUGESAN A, et al. Chronic viral infection compromises the quality of circulating mucosal-invariant T cells and follicular T helper cells via expression of both activating and inhibitory receptors[J]. Res Sq, 2023: rs. 3. rs-rs. 2862719. DOI: 10.21203/rs.3.rs-2862719/v1.
    [18]
    JIANG Y, LI Y, ZHU B. T-cell exhaustion in the tumor microenvironment[J]. Cell Death Dis, 2015, 6( 6): e1792. DOI: 10.1038/cddis.2015.162.
    [19]
    KOCHANOWICZ AM, OSUCH S, BERAK H, et al. Double positive CD4+CD8+(DP) T-cells display distinct exhaustion phenotype in chronic hepatitis C[J]. Cells, 2023, 12( 10): 1446. DOI: 10.3390/cells12101446.
    [20]
    WANG JM, SHI L, MA CJ, et al. Differential regulation of interleukin-12(IL-12)/IL-23 by Tim-3 drives T(H)17 cell development during hepatitis C virus infection[J]. J Virol, 2013, 87( 8): 4372- 4383. DOI: 10.1128/JVI.03376-12.
    [21]
    OKWOR CIA, OH JS, CRAWLEY AM, et al. Expression of inhibitory receptors on T and NK cells defines immunological phenotypes of HCV patients with advanced liver fibrosis[J]. iScience, 2020, 23( 9): 101513. DOI: 10.1016/j.isci.2020.101513.
    [22]
    MOTAMEDI M, SHAHBAZ S, FU L, et al. Galectin-9 expression defines a subpopulation of NK cells with impaired cytotoxic effector molecules but enhanced IFN-γ production, dichotomous to TIGIT, in HIV-1 infection[J]. ImmunoHorizons, 2019, 3( 11): 531- 546. DOI: 10.4049/immunohorizons.1900087.
    [23]
    FERRI S, LONGHI MS, de MOLO C, et al. A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis[J]. Hepatology, 2010, 52( 3): 999- 1007. DOI: 10.1002/hep.23792.
    [24]
    MIGITA K, NAKAMURA M, AIBA Y, et al. Association of soluble T cell immunoglobulin domain and mucin-3(sTIM-3) and mac-2 binding protein glycosylation isomer(M2BPGi) in patients with autoimmune hepatitis[J]. PLoS One, 2020, 15( 12): e0238540. DOI: 10.1371/journal.pone.0238540.
    [25]
    WU HW, TANG SY, ZHOU MY, et al. Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells[J]. FEBS Open Bio, 2021, 11( 5): 1406- 1416. DOI: 10.1002/2211-5463.13148.
    [26]
    HYUN J, HAN J, LEE CB, et al. Pathophysiological aspects of alcohol metabolism in the liver[J]. Int J Mol Sci, 2021, 22( 11): 5717. DOI: 10.3390/ijms22115717.
    [27]
    RIVA A, PALMA E, DEVSHI D, et al. Soluble TIM3 and its ligands galectin-9 and CEACAM1 are in disequilibrium during alcohol-related liver disease and promote impairment of anti-bacterial immunity[J]. Front Physiol, 2021, 12: 632502. DOI: 10.3389/fphys.2021.632502.
    [28]
    POUWELS S, SAKRAN N, GRAHAM Y, et al. Non-alcoholic fatty liver disease(NAFLD): A review of pathophysiology, clinical management and effects of weight loss[J]. BMC Endocr Disord, 2022, 22( 1): 63. DOI: 10.1186/s12902-022-00980-1.
    [29]
    WANG CE, XU WT, GONG J, et al. Treatment of patients with nonalcoholic fatty liver disease[J]. Clin J Med Offic, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.

    王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
    [30]
    DU X, WU Z, XU Y, et al. Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice[J]. Cell Mol Immunol, 2019, 16( 11): 878- 886. DOI: 10.1038/s41423-018-0032-0.
    [31]
    KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18( 3): 151- 166. DOI: 10.1038/s41575-020-00372-7.
    [32]
    BAILLY C. Contribution of the TIM-3/Gal-9 immune checkpoint to tropical parasitic diseases[J]. Acta Trop, 2023, 238: 106792. DOI: 10.1016/j.actatropica.2022.106792.
    [33]
    LIU X, LI C, ZHU J, et al. Dysregulation of FTX/miR-545 signaling pathway downregulates Tim-3 and is responsible for the abnormal activation of macrophage in cirrhosis[J]. J Cell Biochem, 2019, 120( 2): 2336- 2346. DOI: 10.1002/jcb.27562.
    [34]
    LIU SY, XU C, YANG F, et al. Natural killer cells induce CD8+ T cell dysfunction via galectin-9/TIM-3 in chronic hepatitis B virus infection[J]. Front Immunol, 2022, 13: 884290. DOI: 10.3389/fimmu.2022.884290.
    [35]
    HUANG N, ZHOU R, CHEN HY, et al. Splenic CD4+ and CD8+ T-cells highly expressed PD-1 and Tim-3 in cirrhotic patients with HCV infection and portal hypertension[J]. Int J Immunopathol Pharmacol, 2021, 35: 20587384211061051. DOI: 10.1177/20587384211061051.
    [36]
    FADRIQUELA A, KIM CS, LEE KJ, et al. Characteristics of immune checkpoint regulators and potential role of soluble TIM-3 and LAG-3 in male patients with alcohol-associated liver disease[J]. Alcohol, 2022, 98: 9- 17. DOI: 10.1016/j.alcohol.2021.10.002.
    [37]
    DAS M, ZHU C, KUCHROO VK. Tim-3 and its role in regulating anti-tumor immunity[J]. Immunol Rev, 2017, 276( 1): 97- 111. DOI: 10.1111/imr.12520.
    [38]
    GANJALIKHANI HAKEMI M, JAFARINIA M, AZIZI M, et al. The role of TIM-3 in hepatocellular carcinoma: A promising target for immunotherapy?[J]. Front Oncol, 2020, 10: 601661. DOI: 10.3389/fonc.2020.601661.
    [39]
    ZHAO L, JIN Y, YANG C, et al. HBV-specific CD8 T cells present higher TNF-α expression but lower cytotoxicity in hepatocellular carcinoma[J]. Clin Exp Immunol, 2020, 201( 3): 289- 296. DOI: 10.1111/cei.13470.
    [40]
    LIN ZW, JIANG CW, WANG PY, et al. Caveolin-mediated cytosolic delivery of spike nanoparticle enhances antitumor immunity of neoantigen vaccine for hepatocellular carcinoma[J]. Theranostics, 2023, 13( 12): 4166- 4181. DOI: 10.7150/thno.85843.
    [41]
    SONG CH, ZHANG J, WEN RC, et al. Improved anti-hepatocellular carcinoma effect by enhanced Co-delivery of Tim-3 siRNA and sorafenib via multiple pH triggered drug-eluting nanoparticles[J]. Mater Today Bio, 2022, 16: 100350. DOI: 10.1016/j.mtbio.2022.100350.
    [42]
    ZHAO QF, WANG YH, ZHAO BY, et al. Neoantigen immunotherapeutic-gel combined with TIM-3 blockade effectively restrains orthotopic hepatocellular carcinoma progression[J]. Nano Lett, 2022, 22( 5): 2048- 2058. DOI: 10.1021/acs.nanolett.1c04977.
    [43]
    XIE RP, GU MQ, ZHANG FB, et al. Current status and prospect of surgical technique of liver transplantation[J]. Organ Transplant, 2022, 13( 1): 105- 110. DOI: 10.3969/j.issn.1674-7445.2022.01.016

    谢闰鹏, 谷明旗, 张凤博, 等. 肝移植手术技术的现状和展望[J]. 器官移植, 2022, 13( 1): 105- 110. DOI: 10.3969/j.issn.1674-7445.2022.01.016.
    [44]
    QIN L, ZHENG WX, JIANG SM, et al. Noninvasive prediction of immune rejection after liver transplantation with T cell immunoglobulin domain, and mucin domain-3[J]. Transplant Proc, 2022, 54( 7): 1881- 1886. DOI: 10.1016/j.transproceed.2022.04.032.
    [45]
    KOJIMA H, KADONO K, HIRAO H, et al. T cell CEACAM1-TIM-3 crosstalk alleviates liver transplant injury in mice and humans[J]. Gastroenterology, 2023, 165( 5): 1233- 1248. e 9. DOI: 10.1053/j.gastro.2023.07.004
    [46]
    RIFF A, HAEM RAHIMI M, DELIGNETTE MC, et al. Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio[J]. Front Physiol, 2023, 14: 1095723. DOI: 10.3389/fphys.2023.1095723
    [47]
    MYSORE KR, GHOBRIAL RM, KANNANGANAT S, et al. Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections[J]. American Journal of Transplantation, 2018. DOI: info:doi/10.1111/ajt.14546.
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