Liver fibrosis is a repair reaction of the whole body after liver injury caused by many causes (such as viral hepatitis and metabolic dysfunction-associated steatotic liver disease). It is mainly manifested as excessive proliferation and deposition of extracellular matrix in liver tissue, which leads to abnormal changes in liver tissue structure, cirrhosis and liver failure, and affects the normal physiological function of liver. Activated hepatic stellate cells (HSC) are generally considered to be the main cell type that forms liver fibrosis. During liver fibrosis, immune cells play an important role in regulating the activation of HSC, such as interleukin 17 (IL-17), IL- 10 and transforming growth factor β, which are secreted by immune cells in the liver, including helper T cells 17, Th1/Th2 cells, and regulatory T cells. This paper mainly introduces the regulation of T lymphocytes on HSC activation and its impact in fibrosis to expand potential therapeutic approaches to modulate liver fibrosis.
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Effect of T lymphocyte on hepatic stellate cell activation in liver fibrosis
Published on Apr. 25, 2025Total Views: 142 timesTotal Downloads: 65 timesDownloadMobile
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1.Younossi ZM, Wong G, Anstee QM, et al. The global burden of liver disease[J]. Clin Gastroenterol Hepatol, 2023, 21(8): 1978-1991. DOI: 10.1016/j.cgh.2023.04.015.
2.Ezhilarasan D. Hepatic stellate cells in the injured liver: perspectives beyond hepatic fibrosis[J]. J Cell Physiol, 2022, 237(1): 436-449. DOI: 10.1002/jcp.30582.
3.钦圣兰, 吴眉, 周扬, 等. 扶正化瘀方对肝纤维化小鼠外周血及肝内淋巴细胞亚群的影响[J]. 辽宁中医杂志, 2024: 1-12. [Qin SL, Wu M, Zhou Y, et al. The effect of Fuzheng Huayu Fang on peripheral blood and hepatic lymphocyte subsets in mice with liver fibrosis[J]. Liaoning Journal of Traditional Chinese Medicine, 2024: 1-12.] https://www.cnki.com.cn/Article/CJFDTotal-LNZY20240705028.htm.
4.黄辉,徐列明,平键,等. 扶正化瘀方通过改变急性肝损伤小鼠模型肝脏CD8+ T淋巴细胞表型功能预防肝纤维化的价值分析[J]. 临床肝胆病杂志, 2022, 38(2): 342-346. [Huang H, Xu LM, Ping J, et al. Value of Fuzheng Huayu prescription in preventing liver fibrosis by altering the phenotypic function of CD8+ T lym-phocytes in the liver of mice with acute liver injury[J]. Journal of Clinical Hepatology, 2022, 38(2): 342-346.] DOI: 10.3969/j.issn.1001-5256.2022.02.017.
5.Huby T, Gautier EL. Immune cell-mediated features of non-alcoholic steatohepatitis[J]. Nat Rev Immunol, 2022, 22(7): 429-443. DOI: 10.1038/s41577-021-00639-3.
6.Raskov H, Orhan A, Christensen JP, et al. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy[J]. Br J Cancer, 2021, 124(2): 359-367. DOI: 10.1038/s41416-020-01048-4.
7.Wang T, Sun G, Wang Y, et al. The immunoregulatory effects of CD8 T-cell-derived perforin on diet-induced nonalcoholic steatohepatitis[J]. FASEB J, 2019, 33(7): 8490-8503. DOI: 10.1096/fj.201802534RR.
8.Li Y, You Z, Tang R, et al. Tissue-resident memory T cells in chronic liver diseases: phenotype , development and function[J]. Front Immunol, 2022, 13: 967055. DOI: 10.3389/fimmu.2022.967055.
9.Bhattacharjee J, Kirby M, Softic S, et al. Hepatic natural killer T-cell and CD8+ T-cell signatures in mice with nonalcoholic steatohepatitis[J]. Hepatol Commun, 2017, 1(4): 299-310. DOI: 10.1002/hep4.1041.
10.Reeves HL, Friedman SL. Activation of hepatic stellate cells--a key issue in liver fibrosis[J]. Front Biosci, 2002, 7: d808-d826.DOI: 10.2741/reeves.
11.Li X, Zheng Y. Regulatory T cell identity: formation and maintenance[J]. Trends Immunol, 2015, 36(6): 344-353. DOI: 10.1016/j.it.2015.04.006.
12.Lan RY, Cheng C, Lian ZX, et al. Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis[J]. Hepatology, 2006, 43(4): 729-737. DOI: 10.1002/hep.21123.
13.Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(10): 633-646. DOI: 10.1038/s41575-023-00807-x.
14.Ichikawa S, mucida D, tyznik AJ, et al. Hepatic stellate cells function as regulatory bystanders[J]. J Immunol, 2011, 186(10): 5549-5555. DOI: 10.4049/jimmunol.1003917.
15.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.
16.Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm[J]. Nat Rev Immunol, 2004, 4(8): 583-594. DOI: 10.1038/nri1412.
17.Shi Z, Wakil AE, Rockey DC. Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses[J]. Proc Natl Acad Sci U S A, 1997, 94(20): 10663-10668. DOI: 10.1073/pnas.94.20.10663.
18.Knight B, Lim R, Yeoh GC, et al. Interferon-gamma exacerbates liver damage, the hepatic progenitor cell response and fibrosis in a mouse model of chronic liver injury[J]. J Hepatol, 2007, 47(6): 826-833. DOI: 10.1016/j.jhep.2007.06.022.
19.Rau M, Schilling AK, Meertens J, et al. Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis is marked by a higher frequency of Th17 cells in the liver and an increased Th17 / resting regulatory t cell ratio in peripheral blood and in the liver[J]. J Immunol, 2016, 196(1): 97-105. DOI: 10.4049/jimmunol.1501175.
20.Luo XY, Takahara T, Kawai K, et al. IFN-γ deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine-and choline-deficient high-fat diet[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 305(12): G891-G899. DOI: 10.1152/ajpgi.00193.2013.
21.Kokubo K, Onodera A, Kiuchi M, et al. Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis[J]. Front Immunol, 2022, 13: 945063. DOI: 10.3389/fimmu.2022.945063.
22.Gieseck RL 3rd, Wilson MS, Wynn TA. Type 2 immunity in tissue repair and fibrosis[J]. Nat Rev Immunol, 2018, 18(1): 62-76. DOI: 10.1038/nri.2017.90.
23.McKenzie AN. Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13[J]. Pharmacol Ther, 2000, 88(2): 143-151. DOI: 10.1016/s0163-7258(00)00088-7.
24.贾中伟, 储德勇, 王维, 等. HBV感染对日本血吸虫病患者肝纤维化的影响及Th1/Th2型细胞因子水平的变化[J]. 中华检验医学杂志, 2007, 30(10): 1105-1108. [Jia ZW, Chu DY, Wang W, et al. Effects of HBV infection on hepatic fibrosis and level of Th1/Th2 cytokines in the patients with Schistosomiasis japonica[J]. Chinese Journal of Laboratory Medicine, 2007, 30(10): 1105-1108.] DOI: 10.3760/j.issn:1009-9158.2007.10.007.
25.Cayrol C, Girard JP. Interleukin-33 (IL-33): a nuclear cytokine from the IL-1 family[J]. Immunol Rev, 2018, 281(1): 154-168. DOI: 10.1111/imr.12619.
26.Katsarou A, Moustakas II, pyrina I, et al. Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease[J]. World J Gastroenterol, 2020, 26(17): 1993-2011. DOI: 10.3748/wjg.v26.i17.1993.
27.Gao Y, Liu Y, Yang M, et al. IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis[J]. Oncotarget, 2016, 7(23): 33649-33661. DOI: 10.18632/oncotarget.9259.
28.Reißing J, Berres M, Strnad P, et al. Th2 cell activation in chronic liver disease is driven by local IL33 and contributes to IL13-dependent fibrogenesis[J]. Cell Mol Gastroenterol Hepatol, 2024, 17(4): 517-538. DOI: 10.1016/j.jcmgh.2023.12.011.
29.Abdelnabi MN, Hassan GS, Shoukry NH. Role of the type 3 cytokines IL-17 and IL-22 in modulating metabolic dysfunction-associated steatotic liver disease[J]. Front Immunol, 2024, 15: 1437046. DOI: 10.3389/fimmu.2024.1437046.
30.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]. Gastroenterolog, 2012, 143(3): 765-776. e3. DOI: 10.1053/j.gastro.2012.05.049.
31.Lemmers A, Moreno C, Gustot T, et al. The interleukin-17 pathway is involved in human alcoholic liver disease[J]. Hepatology, 2009, 49(2): 646-657. DOI: 10.1002/hep.22680.
32.Tan Z, Qian X, Jiang R, et al. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation[J]. J Immunol, 2013, 191(4): 1835-1844. DOI: 10.4049/jimmunol.1203013.
33.Hwang S, Park S, Yaseen U, et al. KLF10 inhibits TGF-β-mediated activation of hepatic stellate cells via suppression of ATF3 expression[J]. Int J Mol Sci, 2023, 24(16): 12602. DOI: 10.3390/ijms241612602.
34.Mehal W. Mechanisms of liver fibrosis in metabolic syndrome[J]. eGastroenterology, 2023, 1(1): e100015. DOI: 10.1136/egastro- 2023-100015.
35.Rolla S, Alchera E, Imarisio C, et al. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice[J]. Clin Sci (Lond), 2016, 130(3): 193-203. DOI: 10.1042/CS20150405.
36.Kong X, Feng D, Wang H, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice[J]. Hepatology, 2012, 56(3): 1150-1159. DOI: 10.1002/hep.25744.
37.Zhao J, Zhang Z, Luan Y, et al. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment[J]. Hepatology, 2014, 59(4): 1331-1342. DOI: 10.1002/hep.26916.
38.Zhang Y, Cobleigh MA, Lian JQ, et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus[J]. Gastroenterology, 2011, 141(5): 1897-1906. DOI: 10.1053/j.gastro.2011.06.051.
39.Carmo RF, Cavalcanti MSM, Moura P. Role of Interleukin-22 in chronic liver injury[J]. Cytokine, 2017, 98: 107-114. DOI: 10.1016/j.cyto.2016.08.023.
40.栗红江, 胡素玲, 刘洋, 等. 慢性乙型病毒性肝炎患者血清25-羟基维生素D3水平与外周血T淋巴细胞亚群相关性分析 [J]. 临床军医杂志, 2022, 50(2): 205-207, 210. [Li HJ, Hu SL, Liu Y, et al. Correlation analysis between serum 25 hydroxyvitamin D3 levels and peripheral blood T lymphocyte subsets in patients with chronic hepatitis B[J]. Clinical Journal of Medical Officers, 2022, 50(2): 205-207, 210.] DOI: 10.16680/j.1671-3826.2022.02.27.
41.高志远, 何新颖, 许迪, 等. 益肝化湿饮对乙肝肝纤维化患者T淋巴细胞亚群的影响[J]. 中国中西医结合消化杂志, 2023, 31(7): 562-566. [Gao ZY, He XX, Xu D, et al. Influence of Yigan Huashi Decoction on T lymphocyte subsets in patients with hepatitis B liver fibrosis[J]. Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2023, 31(7): 562-566.] DOI: 10.3969/j.issn.1671-038X.2023.07.15.
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