中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

非酒精性脂肪性肝病对肠道免疫细胞的影响

雷亚兰 毕俭 毛靖伟

引用本文:
Citation:

非酒精性脂肪性肝病对肠道免疫细胞的影响

DOI: 10.3969/j.issn.1001-5256.2021.11.039
基金项目: 

国家自然科学基金资助项目 (81500402);

辽宁省自然科学基金资助项目 (20180530055)

详细信息
    通信作者:

    毛靖伟,jingweimao@163.com

  • 中图分类号: R575.5

Impact of nonalcoholic fatty liver disease on intestinal immune cells

Research funding: 

National Natural Science Foundation of China (81500402);

National Natural Science Foundation of Liaoning, China (20180530055)

  • 摘要: 由于肠肝循环以及免疫细胞募集、再循环特性,非酒精性脂肪性肝病(NAFLD)与肠道免疫系统相互影响。肠道免疫失衡促进NAFLD肝脏炎症及纤维化,而NAFLD能够引起肝脏及肠道免疫细胞数量及功能紊乱。主要阐述NAFLD对肠道免疫细胞的影响,简述以肠道免疫细胞为靶点的NAFLD治疗新手段,以期对NAFLD发病及治疗提供新认识。

     

  • [1] COTTER TG, RINELLA M. Nonalcoholic fatty liver disease 2020: The state of the disease[J]. Gastroenterology, 2020, 158(7): 1851-1864. DOI: 10.1053/j.gastro.2020.01.052.
    [2] ZHOU J, ZHOU F, WANG W, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71(5): 1851-1864. DOI: 10.1002/hep.31150.
    [3] ZENG Y, LUO M, PAN L, et al. Vitamin D signaling maintains intestinal innate immunity and gut microbiota: Potential intervention for metabolic syndrome and NAFLD[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 318(3): g542-g553. DOI: 10.1152/ajpgi.00286.2019.
    [4] LUCI C, VIEIRA E, PERCHET T, et al. Natural killer cells and type 1 innate lymphoid cells are new actors in non-alcoholic fatty liver disease[J]. Front Immunol, 2019, 10: 1192. DOI: 10.3389/fimmu.2019.01192.
    [5] SU L, WU Z, CHI Y, et al. Mesenteric lymph node CD4+ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease[J]. Cell Immunol, 2019, 337: 33-41. DOI: 10.1016/j.cellimm.2019.01.005.
    [6] GROSS-VERED M, TRZEBANSKI S, SHEMER A, et al. Defining murine monocyte differentiation into colonic and ileal macrophages[J]. Elife, 2020, 9: e49998. DOI: 10.7554/eLife.49998.
    [7] MAN AL, GICHEVA N, REGOLI M, et al. CX3CR1+ Cell-mediated salmonella exclusion protects the intestinal mucosa during the initial stage of infection[J]. J Immunol, 2017, 198(1): 335-343. DOI: 10.4049/jimmunol.1502559.
    [8] TSUJIMOTO T, KAWARATANI H, KITAZAWA T, et al. Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis[J]. Dig Dis Sci, 2012, 57(5): 1144-1151. DOI: 10.1007/s10620-012-2073-z.
    [9] IMAJO K, FUJITA K, YONEDA M, et al. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling[J]. Cell Metab, 2012, 16(1): 44-54. DOI: 10.1016/j.cmet.2012.05.012.
    [10] ISAACS-TEN A, ECHEANDIA M, MORENO-GONZALEZ M, et al. Intestinal microbiome-macrophage crosstalk contributes to cholestatic liver disease by promoting intestinal permeability in mice[J]. Hepatology, 2020, 72(6): 2090-2108. DOI: 10.1002/hep.31228.
    [11] SCOTT NA, ANDRUSAITE A, ANDERSEN P, et al. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis[J]. Sci Transl Med, 2018, 10(464). DOI: 10.1126/scitranslmed.aao4755.
    [12] SCHULTHESS J, PANDEY S, CAPITANI M, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages[J]. Immunity, 2019, 50(2): 432-445. e7. DOI: 10.1016/j.immuni.2018.12.018.
    [13] DENG M, QU F, CHEN L, et al. SCFA alleviated steatosis and inflammation in mice with NASH induced by MCD[J]. J Endocrinol, 2020, 245(3): 425-437. DOI: 10.1530/JOE-20-0018.
    [14] HUA Y, YANG Y, SUN S, et al. Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells[J]. Sci Rep, 2017, 7(1): 2171. DOI: 10.1038/s41598-017-02415-7.
    [15] STEIMLE A, FRICK JS. Molecular mechanisms of induction of tolerant and tolerogenic intestinal dendritic cells in mice[J]. J Immunol Res, 2016, 2016: 1958650. DOI: 10.1155/2016/1958650.
    [16] TACKE F, YONEYAMA H. From NAFLD to NASH to fibrosis to HCC: Role of dendritic cell populations in the liver[J]. Hepatology, 2013, 58(2): 494-496. DOI: 10.1002/hep.26405.
    [17] ALMEDA-VALDES P, AGUILAR OLIVOS NE, BARRANCO-FRAGOSO B, et al. The role of dendritic cells in fibrosis progression in nonalcoholic fatty liver disease[J]. Biomed Res Int, 2015, 2015: 768071. DOI: 10.1155/2015/768071.
    [18] HEIER EC, MEIER A, JULICH-HAERTEL H, et al. Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis[J]. J Hepatol, 2017, 66(6): 1241-1250. DOI: 10.1016/j.jhep.2017.01.008.
    [19] HENNING JR, GRAFFEO CS, REHMAN A, et al. Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice[J]. Hepatology, 2013, 58(2): 589-602. DOI: 10.1002/hep.26267.
    [20] FANG JH, YU W, ZHOU G, et al. Study on the correlation between small intestinal dendritic cells and non-alcoholic fatty liver disease in mice[J]. Chin J Hepatol, 2019, 27(9): 698-703. DOI: 10.3760/cma.j.issn.1007-3418.2019.09.008.

    方家恒, 喻玮, 周刚, 等. 小鼠小肠树突状细胞与非酒精性脂肪性肝病相关性的研究[J]. 中华肝脏病杂志, 2019, 27(9): 698-703. DOI: 10.3760/cma.j.issn.1007-3418.2019.09.008.
    [21] MAO JW, TANG HY, ZHAO T, et al. Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease[J]. Int J Clin Exp Pathol, 2015, 8(4): 3648-3658.
    [22] FUNG TC, BESSMAN NJ, HEPWORTH MR, et al. Lymphoid-tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism[J]. Immunity, 2016, 44(3): 634-646. DOI: 10.1016/j.immuni.2016.02.019.
    [23] MILLARD AL, MERTES PM, ITTELET D, et al. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages[J]. Clin Exp Immunol, 2002, 130(2): 245-255. DOI: 10.1046/j.0009-9104.2002.01977.x.
    [24] LIU L, LI L, MIN J, et al. Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells[J]. Cell Immunol, 2012, 277(1-2): 66-73. DOI: 10.1016/j.cellimm.2012.05.011.
    [25] VAVASSORI P, MENCARELLI A, RENGA B, et al. The bile acid receptor FXR is a modulator of intestinal innate immunity[J]. J Immunol, 2009, 183(10): 6251-6261. DOI: 10.4049/jimmunol.0803978.
    [26] TOSELLO-TRAMPONT AC, KRUEGER P, NARAYANAN S, et al. NKp46(+) natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice[J]. Hepatology, 2016, 63(3): 799-812. DOI: 10.1002/hep.28389.
    [27] FAN Y, ZHANG W, WEI H, et al. Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment[J]. Liver Int, 2020, 40(3): 598-608. DOI: 10.1111/liv.14307.
    [28] REYNDERS A, YESSAAD N, VU MANH TP, et al. Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt- lymphoid cells[J]. EMBO J, 2011, 30(14): 2934-2947. DOI: 10.1038/emboj.2011.201.
    [29] FORKEL M, BERGLIN L, KEKÄLÄINEN E, et al. Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers[J]. Eur J Immunol, 2017, 47(8): 1280-1294. DOI: 10.1002/eji.201646890.
    [30] WANG S, LI J, WU S, et al. Type 3 innate lymphoid cell: A new player in liver fibrosis progression[J]. Clin Sci (Lond), 2018, 132(24): 2565-2582. DOI: 10.1042/CS20180482.
    [31] WANG Q, LI D, ZHU J, et al. Perforin acts as an immune regulator to prevent the progression of NAFLD[J]. Front Immunol, 2020, 11: 846. DOI: 10.3389/fimmu.2020.00846.
    [32] SU L, WANG JH, CONG X, et al. Intestinal immune barrier integrity in rats with nonalcoholic hepatic steatosis and steatohepatitis[J]. Chin Med J (Engl), 2012, 125(2): 306-311.
    [33] SU L, WU Z, CHI Y, et al. Mesenteric lymph node CD4+ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease[J]. Cell Immunol, 2019, 337: 33-41. DOI: 10.1016/j.cellimm.2019.01.005.
    [34] JIANG W, WU N, WANG X, et al. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease[J]. Sci Rep, 2015, 5: 8096. DOI: 10.1038/srep08096.
    [35] ARPAIA N, CAMPBELL C, FAN X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation[J]. Nature, 2013, 504(7480): 451-455. DOI: 10.1038/nature12726.
    [36] CARPINO G, DEL BEN M, PASTORI D, et al. Increased liver localization of lipopolysaccharides in human and experimental NAFLD[J]. Hepatology, 2020, 72(2): 470-485. DOI: 10.1002/hep.31056.
    [37] WANG X, JI D, ZHU B, et al. Contribution of endotoxin to Th17 bias in patients with non-alcoholic steatohepatitis[J]. Microb Pathog, 2020, 142: 104009. DOI: 10.1016/j.micpath.2020.104009.
    [38] HU Y, ZHANG H, LI J, et al. Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model[J]. J Gastroenterol Hepatol, 2016, 31(3): 676-684. DOI: 10.1111/jgh.13183.
    [39] PABST O, SLACK E. IgA and the intestinal microbiota: The importance of being specific[J]. Mucosal Immunol, 2020, 13(1): 12-21. DOI: 10.1038/s41385-019-0227-4.
    [40] BRUZZÌ S, SUTTI S, GIUDICI G, et al. B2-Lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease (NAFLD)[J]. Free Radic Biol Med, 2018, 124: 249-259. DOI: 10.1016/j.freeradbiomed.2018.06.015.
    [41] MORO-SIBILOT L, BLANC P, TAILLARDET M, et al. Mouse and human liver contain immunoglobulin a-secreting cells originating from peyer's patches and directed against intestinal antigens[J]. Gastroenterology, 2016, 151(2): 311-323. DOI: 10.1053/j.gastro.2016.04.014.
    [42] LI S, WU WC, HE CY, et al. Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats[J]. World J Gastroenterol, 2008, 14(20): 3254-3258. DOI: 10.3748/wjg.14.3254.
    [43] MATSUMOTO K, ICHIMURA M, TSUNEYAMA K, et al. Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis[J]. PLoS One, 2017, 12(6): e0175406. DOI: 10.1371/journal.pone.0175406.
    [44] MCPHERSON S, HENDERSON E, BURT AD, et al. Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease[J]. J Hepatol, 2014, 60(5): 1055-1062. DOI: 10.1016/j.jhep.2014.01.010.
    [45] CATANZARO JR, STRAUSS JD, BIELECKA A, et al. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM[J]. Sci Rep, 2019, 9(1): 13574. DOI: 10.1038/s41598-019-49923-2.
    [46] MIRPURI J, RAETZ M, STURGE CR, et al. Proteobacteria-specific IgA regulates maturation of the intestinal microbiota[J]. Gut Microbes, 2014, 5(1): 28-39. DOI: 10.4161/gmic.26489.
    [47] MOON C, BALDRIDGE MT, WALLACE MA, et al. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation[J]. Nature, 2015, 521(7550): 90-93. DOI: 10.1038/nature14139.
    [48] MICHAIL S, LIN M, FREY MR, et al. Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease[J]. FEMS Microbiol Ecol, 2015, 91(2): 1-9. DOI: 10.1093/femsec/fiu002.
    [49] ISOBE J, MAEDA S, OBATA Y, et al. Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon[J]. Int Immunol, 2020, 32(4): 243-258. DOI: 10.1093/intimm/dxz078.
    [50] KIM M, QIE Y, PARK J, et al. Gut Microbial metabolites fuel host antibody responses[J]. Cell Host Microbe, 2016, 20(2): 202-214. DOI: 10.1016/j.chom.2016.07.001.
    [51] WEINER HL, DA CUNHA AP, QUINTANA F, et al. Oral tolerance[J]. Immunol Rev, 2011, 241(1): 241-259. DOI: 10.1111/j.1600-065X.2011.01017.x.
    [52] LALAZAR G, MIZRAHI M, TURGEMAN I, et al. Oral administration of OKT3 MAb to patients with NASH, promotes regulatory T-cell induction, and alleviates insulin resistance: Results of a phase Ⅱa blinded placebo-controlled trial[J]. J Clin Immunol, 2015, 35(4): 399-407. DOI: 10.1007/s10875-015-0160-6.
    [53] ILAN Y, GINGIS-VELITSKI S, BEN YA'ACO A, et al. A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis[J]. Immunobiology, 2017, 222(3): 544-551. DOI: 10.1016/j.imbio.2016.11.001.
    [54] ILAN Y, BEN YA'ACOV A, SHABBAT Y, et al. Oral administration of a non-absorbable plant cell-expressed recombinant anti-TNF fusion protein induces immunomodulatory effects and alleviates nonalcoholic steatohepatitis[J]. World J Gastroenterol, 2016, 22(39): 8760-8769. DOI: 10.3748/wjg.v22.i39.8760.
    [55] ALMON E, KHOURY T, DRORI A, et al. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase Ⅰ clinical trial using a novel oral anti-TNF alpha-based therapy[J]. J Immunol Methods, 2017, 446: 21-29. DOI: 10.1016/j.jim.2017.03.023.
  • 加载中
计量
  • 文章访问数:  513
  • HTML全文浏览量:  81
  • PDF下载量:  38
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-03-24
  • 录用日期:  2021-04-26
  • 出版日期:  2021-11-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回