Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

Lei Dou; Yoshihiro Ono; Yi-fa Chen; Angus W. Thomson; Xiao-ping Chen

doi:10.1055/s-0038-1646949

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2018; 38(02): 170-180
DOI: 10.1055/s-0038-1646949

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

Lei Dou

¹Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

²Department of Geratology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

,

Yoshihiro Ono

³Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

,

Yi-fa Chen^*

¹Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

,

Angus W. Thomson^*

⁴Starzl Transplantation Institute, Department of Surgery and Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

,

Xiao-ping Chen

¹Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

²Department of Geratology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

› Institutsangaben

Abstract

The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia–reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy.

Keywords

hepatic dendritic cells - liver immunology - tolerance - liver disease

Volltext

Referenzen

References
1 Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol 2013; 14: 996-1006
2 Yokota S, Yoshida O, Ono Y. , et al. Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance. Liver Transpl 2016; 22: 536-546
3 Doherty DG, O'Farrelly C. Innate and adaptive lymphoid cells in the human liver. Immunol Rev 2000; 174: 5-20
4 Liaskou E, Wilson DV, Oo YH. Innate immune cells in liver inflammation. Mediators Inflamm 2012; 201: 949157
5 Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 2010; 10: 753-766
6 Crispe IN. Liver antigen-presenting cells. J Hepatol 2011; 54: 357-365
7 Soysa R, Wu X, Crispe IN. Dendritic cells in hepatitis and liver transplantation. Liver Transpl 2017; 23: 1433-1439
8 Horst AK, Neumann K, Diehl L. , et al. Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells. Cell Mol Immunol 2016; 13: 277-292
9 Merad M, Sathe P, Helft J. , et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31: 563-604
10 Stenger EO, Turnquist HR, Mapara MY. , et al. Dendritic cells and regulation of graft-versus-host disease and graft-versus-leukemia activity. Blood 2012; 119: 5088-5103
11 Soysa DR, Crispe IN. Subcapsular hepatic dendritic cells: hiding in plain sight. Gastroenterology 2016; 151: 1065-1067
12 Matsuno K, Nomiyama H, Yoneyama H. , et al. Kupffer cell-mediated recruitment of dendritic cells to the liver crucial for a host defense. Dev Immunol 2002; 9: 143-149
13 Yoneyama H, Matsuno K, Zhang Y. , et al. Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 2001; 193: 35-49
14 Matsuno K, Ezaki T. Dendritic cell dynamics in the liver and hepatic lymph. Int Rev Cytol 2000; 197: 83-136
15 Kudo S, Matsuno K, Ezaki T. , et al. A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation. J Exp Med 1997; 185: 777-784
16 Steptoe RJ, Fu F, Li W. , et al. Augmentation of dendritic cells in murine organ donors by Flt3 ligand alters the balance between transplant tolerance and immunity. J Immunol 1997; 159: 5483-5491
17 Drakes ML, Lu L, Subbotin VM. , et al. In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver. J Immunol 1997; 159: 4268-4278
18 Chen K, Wang JM, Yuan R. , et al. Tissue-resident dendritic cells and diseases involving dendritic cell malfunction. Int Immunopharmacol 2016; 34: 1-15
19 David BA, Rezende RM, Antunes MM. , et al. Combination of Mass cytometry and imaging analysis reveals origin, location, and functional repopulation of liver myeloid cells in mice. Gastroenterology 2016; 151: 1176-1191
20 Krueger PD, Kim TS, Sung SS. , et al. Liver-resident CD103+ dendritic cells prime antiviral CD8+ T cells in situ. J Immunol 2015; 194: 3213-3222
21 Reizis B, Bunin A, Ghosh HS. , et al. Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol 2011; 29: 163-183
22 Matta BM, Castellaneta A, Thomson AW. Tolerogenic plasmacytoid DC. Eur J Immunol 2010; 40: 2667-2676
23 Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol 2015; 15: 471-485
24 Schlitzer A, McGovern N, Teo P. , et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 2013; 38: 970-983
25 Nizzoli G, Krietsch J, Weick A. , et al. Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. Blood 2013; 122: 932-942
26 Haniffa M, Shin A, Bigley V. , et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 2012; 37: 60-73
27 Wang J, Kubes P. A reservoir of mature cavity macrophages that can rapidly invade visceral organs to affect tissue repair. Cell 2016; 165: 668-678
28 Medina KL, Tangen SN, Seaburg LM. , et al. Separation of plasmacytoid dendritic cells from B-cell-biased lymphoid progenitor (BLP) and Pre-pro B cells using PDCA-1. PLoS One 2013; 8: e78408
29 Castellaneta A, Yoshida O, Kimura S. , et al. Plasmacytoid dendritic cell-derived IFN-alpha promotes murine liver ischemia/reperfusion injury by induction of hepatocyte IRF-1. Hepatology 2014; 60: 267-277
30 Lu L, Woo J, Rao AS. , et al. Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen. J Exp Med 1994; 179: 1823-1834
31 Lukacs-Kornek V, Schuppan D. Dendritic cells in liver injury and fibrosis: shortcomings and promises. J Hepatol 2013; 59: 1124-1126
32 Raich-Regue D, Glancy M, Thomson AW. Regulatory dendritic cell therapy: from rodents to clinical application. Immunol Lett 2014; 161: 216-221
33 Castellaneta A, Sumpter TL, Chen L. , et al. NOD2 ligation subverts IFN-alpha production by liver plasmacytoid dendritic cells and inhibits their T cell allostimulatory activity via B7–H1 up-regulation. J Immunol 2009; 183: 6922-6932
34 Manicassamy S, Pulendran B. Dendritic cell control of tolerogenic responses. Immunol Rev 2011; 241: 206-227
35 Ibrahim J, Nguyen AH, Rehman A. , et al. Dendritic cell populations with different concentrations of lipid regulate tolerance and immunity in mouse and human liver. Gastroenterology 2012; 143: 1061-1072
36 van der Aa E, Buschow SI, Biesta PJ. , et al. The effect of chronic hepatitis B virus infection on BDCA3+ dendritic cell frequency and function. PLoS One 2016; 11: e0161235
37 Lambotin M, Raghuraman S, Stoll-Keller F. , et al. A look behind closed doors: interaction of persistent viruses with dendritic cells. Nat Rev Microbiol 2010; 8: 350-360
38 Nakai M, Oshiumi H, Funami K. , et al. Interferon (IFN) and cellular immune response evoked in RNA-pattern sensing during infection with hepatitis C virus (HCV). Sensors (Basel) 2015; 15: 27160-27173
39 Velazquez VM, Hon H, Ibegbu C. , et al. Hepatic enrichment and activation of myeloid dendritic cells during chronic hepatitis C virus infection. Hepatology 2012; 56: 2071-2081
40 Cervantes-Barragan L, Lewis KL, Firner S. , et al. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc Natl Acad Sci U S A 2012; 109: 3012-3017
41 Lee J, Suh WI, Shin EC. T-cell dysfunction and inhibitory receptors in hepatitis C virus infection. Immune Netw 2010; 10: 120-125
42 Zhang S, Kodys K, Li K. , et al. Human type 2 myeloid dendritic cells produce interferon-lambda and amplify interferon-alpha in response to hepatitis C virus infection. Gastroenterology 2013; 144: 414-425
43 Sehgal M, Khan ZK, Talal AH. , et al. Dendritic cells in HIV-1 and HCV infection: can they help win the battle?. Virology (Auckl) 2013; 4: 1-25
44 Zhai Y, Busuttil RW, Kupiec-Weglinski JW. Liver ischemia and reperfusion injury: new insights into mechanisms of innate-adaptive immune-mediated tissue inflammation. Am J Transplant 2011; 11: 1563-1569
45 Eltzschig HK, Eckle T. Ischemia and reperfusion–from mechanism to translation. Nat Med 2011; 17: 1391-1401
46 Nace GW, Huang H, Klune JR. , et al. Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice. Hepatology 2013; 58: 374-387
47 Bamboat ZM, Ocuin LM, Balachandran VP. , et al. Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion. J Clin Invest 2010; 120: 559-569
48 Zhai Y, Qiao B, Gao F. , et al. Type I, but not type II, interferon is critical in liver injury induced after ischemia and reperfusion. Hepatology 2008; 47: 199-206
49 Huang B, Qi ZT, Xu Z. , et al. Global characterization of interferon regulatory factor (IRF) genes in vertebrates: glimpse of the diversification in evolution. BMC Immunol 2010; 11: 22
50 Ueki S, Dhupar R, Cardinal J. , et al. Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury. Hepatology 2010; 51: 1692-1701
51 Klune JR, Dhupar R, Kimura S. , et al. Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 2012; 303: G666-G673
52 Taniguchi T, Ogasawara K, Takaoka A. , et al. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol 2001; 19: 623-655
53 Idzko M, Ferrari D, Eltzschig HK. Nucleotide signalling during inflammation. Nature 2014; 509: 310-317
54 Burnstock G, Boeynaems JM. Purinergic signalling and immune cells. Purinergic Signal 2014; 10: 529-564
55 Novitskiy SV, Ryzhov S, Zaynagetdinov R. , et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 2008; 112: 1822-1831
56 Chouker A, Ohta A, Martignoni A. , et al. In vivo hypoxic preconditioning protects from warm liver ischemia-reperfusion injury through the adenosine A2B receptor. Transplantation 2012; 94: 894-902
57 Mandili G, Alchera E, Merlin S. , et al. Mouse hepatocytes and LSEC proteome reveal novel mechanisms of ischemia/reperfusion damage and protection by A2aR stimulation. J Hepatol 2015; 62: 573-580
58 Yoshida O, Kimura S, Jackson EK. , et al. CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia-reperfusion injury in mice. Hepatology 2013; 58: 2163-2175
59 Yoneyama H, Ichida T. Recruitment of dendritic cells to pathological niches in inflamed liver. Med Mol Morphol 2005; 38: 136-141
60 Funken D, Ishikawa-Ankerhold H, Uhl B. , et al. In situ targeting of dendritic cells sets tolerogenic environment and ameliorates CD4(+) T-cell response in the postischemic liver. FASEB J 2017; 31: 4796-4808
61 Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134: 1655-1669
62 Connolly MK, Bedrosian AS, Mallen-St Clair J. , et al. In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-alpha. J Clin Invest 2009; 119: 3213-3225
63 Sumpter TL, Dangi A, Matta BM. , et al. Hepatic stellate cells undermine the allostimulatory function of liver myeloid dendritic cells via STAT3-dependent induction of IDO. J Immunol 2012; 189: 3848-3858
64 Cheng JT, Deng YN, Yi HM. , et al. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis 2016; 5: e198
65 Pradere JP, Kluwe J, De Minicis S. , et al. Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice. Hepatology 2013; 58: 1461-1473
66 Duarte S, Baber J, Fujii T. , et al. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol 2015; 44: 147-156
67 Osman M, Tortorella M, Londei M. , et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells. Immunology 2002; 105: 73-82
68 Jiao J, Sastre D, Fiel MI. , et al. Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression. Hepatology 2012; 55: 244-255
69 Heier EC, Meier A, Julich-Haertel H. , et al. Murine CD103(+) dendritic cells protect against steatosis progression towards steatohepatitis. J Hepatol 2017; 66: 1241-1250
70 Sachdeva M, Chawla YK, Arora SK. Immunology of hepatocellular carcinoma. World J Hepatol 2015; 7: 2080-2090
71 Bertino G, Demma S, Ardiri A. , et al. The immune system in hepatocellular carcinoma and potential new immunotherapeutic strategies. BioMed Res Int 2015; 201: 731469
72 Kim R, Emi M, Tanabe K. Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunity. Clin Exp Immunol 2006; 146: 189-196
73 Hwu P, Du MX, Lapointe R. , et al. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 2000; 164: 3596-3599
74 Dudek AM, Martin S, Garg AD. , et al. Immature, semi-mature, and fully mature dendritic cells: toward a DC-cancer cells interface that augments anticancer immunity. Front Immunol 2013; 4: 438
75 Ouyang FZ, Wu RQ, Wei Y. , et al. Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma. Nat Commun 2016; 7: 13453
76 Lee JH, Lee Y, Lee M. , et al. A phase I/IIa study of adjuvant immunotherapy with tumour antigen-pulsed dendritic cells in patients with hepatocellular carcinoma. Br J Cancer 2015; 113: 1666-1676
77 Pardee AD, Yano H, Weinstein AM. , et al. Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma. J Immunother Cancer 2015; 3: 32
78 Tada F, Abe M, Hirooka M. , et al. Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma. Int J Oncol 2012; 41: 1601-1609
79 Shang N, Figini M, Shangguan J. , et al. Dendritic cells based immunotherapy. Am J Cancer Res 2017; 7: 2091-2102
80 Jung NC, Lee JH, Choi HJ. , et al. Dendritic cell immunotherapy combined with cytokine-induced killer cells effectively suppresses established hepatocellular carcinomas in mice. Immunol Invest 2016; 45: 553-565
81 Calne RY, Sells RA, Pena JR. , et al. Induction of immunological tolerance by porcine liver allografts. Nature 1969; 223: 472-476
82 Kamada N. Transplantation tolerance and immunosuppression following liver grafting in rats. Immunol Today 1985; 6: 336-342
83 Qian S, Demetris AJ, Murase N. , et al. Murine liver allograft transplantation: tolerance and donor cell chimerism. Hepatology 1994; 19: 916-924
84 Sanchez-Fueyo A, Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology 2011; 140: 51-64
85 Taner T, Park WD, Stegall MD. Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation. Kidney Int 2017; 91: 1193-1202
86 Wong TW, Gandhi MJ, Daly RC. , et al. Liver allograft provides immunoprotection for the cardiac allograft in combined heart-liver transplantation. Am J Transplant 2016; 16: 3522-3531
87 Qian S, Lu L, Fu F. , et al. Apoptosis within spontaneously accepted mouse liver allografts: evidence for deletion of cytotoxic T cells and implications for tolerance induction. J Immunol 1997; 158: 4654-4661
88 Tay SS, Lu B, Sierro F. , et al. Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation. Liver Transpl 2013; 19: 1224-1235
89 Li W, Lu L, Wang Z. , et al. Il-12 antagonism enhances apoptotic death of T cells within hepatic allografts from Flt3 ligand-treated donors and promotes graft acceptance. J Immunol 2001; 166: 5619-5628
90 Iwasaki Y, Fujio K, Okamura T. , et al. Interleukin-27 in T cell immunity. Int J Mol Sci 2015; 16: 2851-2863
91 Mascanfroni ID, Yeste A, Vieira SM. , et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 2013; 14: 1054-1063
92 Matta BM, Raimondi G, Rosborough BR. , et al. IL-27 production and STAT3-dependent upregulation of B7–H1 mediate immune regulatory functions of liver plasmacytoid dendritic cells. J Immunol 2012; 188: 5227-5237
93 Bhatt S, Qin J, Bennett C. , et al. All-trans retinoic acid induces arginase-1 and inducible nitric oxide synthase-producing dendritic cells with T cell inhibitory function. J Immunol 2014; 192: 5098-5108
94 Yoshida O, Kimura S, Dou L. , et al. DAP12 deficiency in liver allografts results in enhanced donor DC migration, augmented effector T cell responses and abrogation of transplant tolerance. Am J Transplant 2014; 14: 1791-1805
95 Ito T, Yang M, Wang YH. , et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 2007; 204: 105-115
96 Campana S, De Pasquale C, Carrega P. , et al. Cross-dressing: an alternative mechanism for antigen presentation. Immunol Lett 2015; 168: 349-354
97 Liu Q, Rojas-Canales DM, Divito SJ. , et al. Donor dendritic cell-derived exosomes promote allograft-targeting immune response. J Clin Invest 2016; 126: 2805-2820
98 Marino J, Babiker-Mohamed MH, Crosby-Bertorini P. , et al. Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation. Sci Immunol 2016; 1: aaf8759
99 Ono Y, Perez-Gutierrez A, Nakao T. , et al. Graft-infiltrating PD-L1(hi) cross-dressed dendritic cells regulate anti-donor T cell responses in mouse liver transplant tolerance. Hepatology 2018; 67: 1499-1515
100 Witek RP, Yang L, Liu R. , et al. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells. Gastroenterology 2009; 136: 320-330
101 Masyuk AI, Masyuk TV, Larusso NF. Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. J Hepatol 2013; 59: 621-625
102 Chen L, Chen R, Kemper S. , et al. Suppression of fibrogenic signaling in hepatic stellate cells by Twist1-dependent microRNA-214 expression: role of exosomes in horizontal transfer of Twist1. Am J Physiol Gastrointest Liver Physiol 2015; 309: G491-G499
103 Szabo G, Momen-Heravi F. Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets. Nat Rev Gastroenterol Hepatol 2017; 14: 455-466
104 Manz MG, Traver D, Akashi K. , et al. Dendritic cell development from common myeloid progenitors. Ann N Y Acad Sci 2001; 938: 167-173
105 Fogg DK, Sibon C, Miled C. , et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 2006; 311: 83-87
106 Naik SH, Sathe P, Park HY. , et al. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 2007; 8: 1217-1226
107 Liu K, Victora GD, Schwickert TA. , et al. In vivo analysis of dendritic cell development and homeostasis. Science 2009; 324: 392-397
108 Varol C, Vallon-Eberhard A, Elinav E. , et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 2009; 31: 502-512
109 Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 2009; 27: 669-692
110 Miller JC, Brown BD, Shay T. , et al. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 2012; 13: 888-899
111 Collin M, Bigley V. Human dendritic cell subsets: an update. Immunology 2018; 154: 3-20