Role and mechanism of action of intrahepatic intrinsic antigen-presenting cells in regulating anti-hepatitis B virus immune response
-
摘要:
肝脏具有独特的免疫微环境,其内固有的抗原递呈细胞构成相互协作的网络,精密调控着肝脏免疫耐受和免疫应答之间的平衡。在HBV感染过程中,一方面病毒可利用肝内固有抗原递呈细胞诱导免疫耐受的特性逃避免疫系统对其的清除效应,形成持续性感染;另一方面,肝内固有抗原递呈细胞的功能成熟和活化也可介导有效抗乙型肝炎免疫应答的发生,从而清除病毒感染。就肝内固有抗原递呈细胞调控抗乙型肝炎免疫应答的作用及机制研究进展加以阐述。
Abstract:The liver has a unique immune microenvironment, and the intrinsic antigen-presenting cells in the liver interact with each other and form a network to accurately regulate the homeostasis between liver immune tolerance and immune response. During hepatitis B virus(HBV) infection, on the one hand, the intrahepatic intrinsic antigen-presenting cells induce immune tolerance to help the virus escape immune clearance and thus result in persistent infection; on the other hand, the maturation and activation of the intrahepatic intrinsic antigen-presenting cells can also mediate effective anti-HBV immune response to achieve virus clearance. This article elaborates on the research advances in the role and mechanism of action of intrahepatic intrinsic antigen-presenting cells in regulating immune response against HBV infection.
-
[1] LU FM, ZHUANG H. Management of hepatitis B in China[J].Chin Med J, 2009, 122(1):3-4. [2] JENNE CN, KUBES P. Immune surveillance by the liver[J].Nat Immunol, 2013, 14(10):996-1006. [3] THOMSON AW, KNOLLE PA. Antigen-presenting cell function in the tolerogenic liver environment[J]. Nat Rev Immunol,2010, 10(11):753-766. [4] ADKINS B, BU Y, GUEVARA P. Murine neonatal CD4+lymph node cells are highly deficient in the development of antigenspecific Th1 function in adoptive adult hosts[J]. J Immunol,2002, 169(9):4998-5004. [5] CARAMBIA A, FREUND B, SCHWINGE D, et al. TGF-β-dependent induction of CD4+CD25+Foxp3+Tregs by liver sinusoidal endothelial cells[J]. J Hepatol, 2014, 61(3):594-599. [6] LIMMER A, OHL J, KURTS C, et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+T cells results in antigen-specific T-cell tolerance[J]. Nat Med,2000, 6(12):1348-1354. [7] LOHSE AW, KNOLLE PA, BILO K, et al. Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells[J]. Gastroenterology, 1996, 110(4):1175-1181. [8] SCHURICH A, BÖTTCHER JP, BURGDORF S, et al. Ditinct kinetics and dynamics of cross-presentation in liver sinusoidal endothelial cells compared to dendritic cells[J]. Hepatology,2009, 50(3):909-919. [9] von OPPEN N, SCHURICH A, HEGENBARTH S, et al. Systemic antigen cross-presented by liver sinusoidal endothelial cells induces liver-specific CD8 T-cell retention and tolerization[J]. Hepatology, 2009, 49(5):1664-1672. [10] DIEHL L, SCHURICH A, GROCHTMANN R, et al. Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+T cell tolerance[J]. Hepatology, 2008, 47(1):296-305. [11] LU Y, WANG B, HUANG H, et al. The interferon-alpha gene family of Marmota himalayana, a Chinese marmot species with susceptibility to woodchuck hepatitis virus infection[J]. Dev Comp Immunol, 2008, 32(4):445-457. [12] LIU J, JIANG M, MA Z, et al. TLR1/2 ligand-stimulated mouse liver endothelial cel s secrete IL-12 and trigger CD8+T cell immunity in vitro[J]. J Immunol, 2013, 191(12):6178-6190. [13] UHRIG A, BANAFSCHE R, KREMER M, et al. Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver[J]. J Leukoc Biol, 2005, 77(5):626-633. [14] KNOLLE PA, SCHMITT E, JIN S, et al. Induction of cytokine production in naive CD4(+)T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 cells[J]. Gastroenterology, 1999, 116(6):1428-1440. [15] SCHILDBERG FA, HEGENBARTH SI, SCHUMAK B, et al. Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells[J]. Eur J Immunol, 2008,38(4):957-967. [16] KNOLLE PA, UHRIG A, HEGENBARTH S, et al. IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules[J]. Clin Exp Immunol, 1998, 114(3):427-433. [17] NURIEVA R, THOMAS S, NGUYEN T, et al. T-cell tolerance or function is determined by combinatorial costimulatory signals[J]. EMBO J, 2006, 25(11):2623-2633. [18] SCHURICH A, BERG M, STABENOW D, et al. Dynamic regulation of CD8 T cell tolerance induction by liver sinusoidal endothelial cells[J]. J Immunol, 2010, 184(8):4107-4114. [19] KERN M, POPOV A, SCHOLZ K, et al. Virally infected mouse liver endothelial cells trigger CD8+T-cell immunity[J]. Gastroenterology, 2010, 138(1):336-346. [20] BÖTTCHER JP, SCHANZ O, WOHLLEBER D, et al. Liverprimed memory T cells generated under noninflammatory conditions provide anti-infectious immunity[J]. Cell Rep, 2013,3(3):779-795. [21] BÖTTCHER JP, SCHANZ O, GARBERS C, et al. IL-6 transsignaling-dependent rapid development of cytotoxic CD8+T cell function[J]. Cell Rep, 2014, 8(5):1318-1327. [22] WITTLICH M, DUDEK M, BÖTTCHER JP, et al. Liver sinusoidal endothelial cell cross-priming is supported by CD4 T cell-derived IL-2[J]. J Hepatol, 2017, 66(5):978-986. [23] HUANG S, ZOU S, CHEN M, et al. Local stimulation of liver sinusoidal endothelial cells with a NOD1 agonist activates T cells and suppresses hepatitis B virus replication in mice[J].J Immunol, 2018, 200(9):3170-3179. [24] HUANG S, WU J, GAO X, et al. LSECs express functional NOD1 receptors:A role for NOD1 in LSEC maturation-induced T cell immunity in vitro[J]. Mol Immunol, 2018, 101:167-175. [25] YANG S, WANG L, PAN W, et al. MMP2/MMP9-mediated CD100 shedding is crucial for inducing intrahepatic anti-HBV CD8 T cell responses and HBV clearance[J]. J Hepatol,2019, 71(4):685-698. [26] GUIDOTTI LG, INVERSO D, SIRONI L, et al. Immunosurveillance of the liver by intravascular effector CD8(+)T cells[J].Cell, 2015, 161(3):486-500. [27] MASS E, BALLESTEROS I, FARLIK M, et al. Specification of tissue-resident macrophages during organogenesis[J]. Science, 2016, 353(6304):aaf4238. [28] INABA K, WITMER-PACK M, INABA M, et al. The tissue distribution of the B7-2 costimulator in mice:Abundant expression on dendritic cells in situ and during maturation in vitro[J]. J Exp Med, 1994, 180(5):1849-1860. [29] RUBINSTEIN D, ROSKA AK, LIPSKY PE. Antigen presentation by liver sinusoidal lining cells after antigen exposure in vivo[J]. J Immunol, 1987, 138(5):1377-1382. [30] ROLAND CR, MANGINO MJ, DUFFY BF, et al. Lymphocyte suppression by Kupffer cells prevents portal venous tolerance induction:A study of macrophage function after intravenous gadolinium[J]. Transplantation, 1993, 55(5):1151-1158. [31] GUIDOTTI LG, BORROW P, BROWN A, et al. Noncytopathic clearance of lymphocytic choriomeningitis virus from the hepatocyte[J]. J Exp Med, 1999, 189(10):1555-1564. [32] PASQUETTO V, GUIDOTTI LG, KAKIMI K, et al. Host-virus interactions during malaria infection in hepatitis B virus transgenic mice[J]. J Exp Med, 2000, 192(4):529-536. [33] XU L, YIN W, SUN R, et al. Kupffer cell-derived IL-10plays a key role in maintaining humoral immune tolerance in hepatitis B virus-persistent mice[J]. Hepatology, 2014, 59(2):443-452. [34] LOKHONINA A, ELCHANINOV A, FATKHUDINOV T, et al.Activated macrophages of monocytic origin predominantly express proinflammatory cytokine genes, whereas kupffer cells predominantly express anti-inflammatory cytokine genes[J].Biomed Res Int, 2019, 2019:3912142. [35] YOU Q, CHENG L, KEDL RM, et al. Mechanism of T cell tolerance induction by murine hepatic Kupffer cells[J]. Hepatology, 2008, 48(3):978-990. [36] KNOLLE P, SCHLAAK J, UHRIG A, et al. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide(LPS)challenge[J]. J Hepatol, 1995, 22(2):226-229. [37] LIU J, YU Q, WU W, et al. TLR2 Stimulation strengthens intrahepatic myeloid-derived cell-mediated T cell tolerance through inducing Kupffer cell expansion and IL-10 production[J]. J Immunol, 2018, 200(7):2341-2351. [38] BURGIO VL, BALLARDINI G, ARTINI M, et al. Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology[J]. Hepatology, 1998, 27(6):1600-1606. [39] TIAN Y, KUO CF, AKBARI O, et al. Maternal-derived hepatitis B virus e antigen alters macrophage function in offspring to drive viral persistence after vertical transmission[J]. Immunity, 2016, 44(5):1204-1214. [40] WU LL, PENG WH, WU HL, et al. Lymphocyte antigen 6complex, locus C+monocytes and Kupffer cells orchestrate liver immune responses against hepatitis B virus in mice[J].Hepatology, 2019, 69(6):2364-2380. [41] CHOU HH, CHIEN WH, WU LL, et al. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota[J]. Proc Natl Acad Sci U S A, 2015,112(7):2175-2180. [42] LI M, SUN R, XU L, et al. Kupffer cells support hepatitis B virus-mediated CD8+T cell exhaustion via hepatitis B core antigen-TLR2 interactions in mice[J]. J Immunol, 2015, 195(7):3100-3109. [43] CHENG X, XIA Y, SERTI E, et al. Hepatitis B virus evades innate immunity of hepatocytes but activates cytokine production by macrophages[J]. Hepatology, 2017, 66(6):1779-1793. [44] TAY SS, WONG YC, ROEDIGER B, et al. Intrahepatic activation of naive CD4+T cells by liver-resident phagocytic cells[J]. J Immunol, 2014, 193(5):2087-2095. [45] BOLTJES A, van MONTFOORT N, BIESTA PJ, et al. Kupffer cells interact with hepatitis B surface antigen in vivo and in vitro, leading to proinflammatory cytokine production and natural killer cell function[J]. J Infect Dis, 2015, 211(8):1268-1278. [46] HÖSEL M, QUASDORFF M, WIEGMANN K, et al. Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection[J]. Hepatology, 2009, 50(6):1773-1782. [47] LIU C, HUANG X, WERNER M, et al. Elevated expression of chemokine CXCL13 in chronic hepatitis B patients links to immune control during antiviral therapy[J]. Front Immunol,2017, 8:323. [48] LE COUTEUR DG, COGGER VC, MARKUS AM, et al. Pseudocapillarization and associated energy limitation in the aged rat liver[J]. Hepatology, 2001, 33(3):537-543. [49] WARREN A, LE COUTEUR DG, FRASER R, et al. T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells[J]. Hepatology, 2006, 44(5):1182-1190. [50] CHEN M, TABACZEWSKI P, TRUSCOTT SM, et al. Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin,and low molecular weight polypeptide proteasome subunit components of antigen processing and presentation pathway[J]. J Immunol, 2005, 175(2):1047-1055. [51] BÉNÉCHET AP, de SIMONE G, DI LUCIA P, et al. Dynamics and genomic landscape of CD8+T cells undergoing hepatic priming[J]. Nature, 2019, 574(7777):200-205. [52] WINAU F, HEGASY G, WEISKIRCHEN R, et al. Ito cells are liver-resident antigen-presenting cells for activating T cell responses[J]. Immunity, 2007, 26(1):117-129. [53] YU X, LAN P, HOU X, et al. HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1βproduction via suppressing the NF-κB pathway and ROS production[J]. J Hepatol, 2017, 66(4):693-702.
计量
- 文章访问数: 1104
- HTML全文浏览量: 21
- PDF下载量: 236
- 被引次数: 0