Immunology of the gut and liver: A love/hate relationship

Gut

Volumn 57, Issue 6, 2008, Pages 838-848

  Adams, D H ^a   Eksteen, B ^a   Curbishley, S M ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

NONSTEROID ANTIINFLAMMATORY AGENT;

ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; CELIAC DISEASE; CELL MIGRATION; DENDRITIC CELL; ENDOTHELIUM CELL; ENTERITIS; EPITHELIUM; GRAFT VERSUS HOST REACTION; HEPATITIS; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; IMMUNOREGULATION; INTESTINE; INTESTINE INFECTION; LAMINA PROPRIA; LIVER; LIVER CELL; LIVER FUNCTION; LYMPHOCYTE FUNCTION; LYMPHOCYTE TRANSFER; OUTCOME ASSESSMENT; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE ACTIVATION;

ANTIGEN PRESENTATION; GASTROINTESTINAL DISEASES; GASTROINTESTINAL TRACT; HUMANS; IMMUNE TOLERANCE; IMMUNITY, MUCOSAL; INTESTINAL MUCOSA; LIVER; LIVER DISEASES;

EID: 44149106177     PISSN: 00175749     EISSN: None     Source Type: Journal    
DOI: 10.1136/gut.2007.122168     Document Type: Review

References (160)

1. MacDonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005;307:1920-5.
2. Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003;3:331-41.
3. Crispe IN, Giannandrea M, Klein I, et al. Cellular and molecular mechanisms of liver tolerance. Immunol Rev 2006;213:101- 18.
4. Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 2006;6:244-51.
5. Nagler-Anderson C. Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol 2001;1:59-67.
6. Ayabe T, Satchell DP, Wilson CL, et al. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000;1:113-8.
7. Macpherson AJ, Gatto D, Sainsbury E, et al. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 2000;288:2222-6.
8. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-80.
9. Strober W, Murray PJ, Kitani A, et al. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 2006;6:9-20.
10. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001;411:599-603.
11. Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol 2006;6:476-83.
12. Huang FP, Platt N, Wykes M, et al. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med 2000;191:435-44.
13. Yrlid U, Milling SW, Miller JL, et al. Regulation of intestinal dendritic cell migration and activation by plasmacytoid dendritic cells, TNF-alpha and type 1 IFNs after feeding a TLR7/8 ligand. J Immunol 2006;176:5205-12.
14. Yrlid U, Cerovic V, Milling S, et al. Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph. J Immunol 2006;177:6115-21.
15. Wendland M, Czeloth N, Mach N, et al. CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine. Proc Natl Acad Sci U S A 2007;104:6347-52.
16. Moseman EA, Liang X, Dawson AJ, et al. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J Immunol 2004;173:4433-42.
17. Castellaneta A, Abe M, Morelli AE, et al. Identification and characterization of intestinal Peyer's patch interferon-alpha producing (plasmacytoid) dendritic cells. Hum Immunol 2004;65:104-13.
18. Lai WK, Curbishley SM, Goddard S, et al. Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell function. J Hepatol 2007;47:338-47.
19. Lian ZX, Okada T, He XS, et al. Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations. J Immunol 2003;170:2323-30.
20. Niess JH, Brand S, Gu X, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 2005;307:254-8.
21. Rescigno M, Urbano M, Valzasina B, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001;2:361-7.
22. Ericsson A, Svensson M, Arya A, et al. CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes. Eur J Immunol 2004;34:2720-9.
23. Cepek KL, Shaw SK, Parker CM, et al. Adhesion between epithelial-cells and T-lymphocytes mediated by E-cadherin and the alpha(e)beta(7) integrin. Nature 1994;372:190-3.
24. El-Asady R, Yuan R, Liu K, et al. TGF-{beta}-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease. J Exp Med 2005;201:1647-57.
25. Hayday AC. [gamma][delta] cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 2000;18:975-1026.
26. Saada JI, Pinchuk IV, Barrera CA, et al. Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. J Immunol 2006;177:5968-79.
27. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531-62.
28. Westendorf AM, Templin M, Geffers R, et al. CD4+ T cell mediated intestinal immunity: chronic inflammation versus immune regulation. Gut 2005;54:60-9.
29. Makita S, Kanai T, Nemoto Y, et al. Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation. J Immunol 2007;178:4937-46.
30. Sun CM, Hall JA, Blank RB, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007;204:1775-85.
31. Coombes JL, Siddiqui KR, rancibia-Carcamo CV, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-{beta}- and retinoic acid-dependent mechanism. J Exp Med 2007;204:1757-64.
32. Campbell JJ, Butcher EC. Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 2000;12:336-41.
33. Agace WW. Tissue-tropic effector T cells: generation and targeting opportunities. Nat Rev Immunol 2006;6:682-92.
34. Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol 1997;151:97-110.
35. Kunkel EJ, Campbell JJ, Haraldsen G, et al. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med 2000;192:761-8.
36. Papadakis KA, Prehn J, Nelson V, et al. The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J Immunol 2000;165:5069-76.
37. Eksteen B, Grant AJ, Miles A, et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med 2004;200:1511-7.
38. Stenstad H, Ericsson A, Johansson-Lindbom B, et al. Gut associated lymphoid tissue primed CD4+ T cells display CCR9 dependent and independent homing to the small intestine. Blood 2006.
39. ChemoCentryx. Traficet EN. www.chemocentryx.com. Ref Type: Generic, 2006.
40. Ghosh S. Therapeutic value of alpha-4 integrin blockade in inflammatory bowel disease:the role of natalizumab. Expert Opin Biol Ther 2003;3:995-1000.
41. Rivera-Nieves J, Ho J, Bamias G, et al. Antibody blockade of CCL25/CCR9 ameliorates early but not late chronic murine ileitis. Gastroenterology 2006;131:1518-29.
42. Mora JR, Iwata M, Eksteen B, et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 2006;314:1157-60.
43. Mora JR, Bono MR, Manjunath N, et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 2003;424:88-93.
44. Johansson-Lindbom B, Svensson M, Wurbel MA, et al. Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant. J Exp Med 2003;198:963-9.
45. Stagg AJ, Kamm MA, Knight SC. Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur J Immunol 2002;32:1445-54.
46. Iwata M, Hirakiyama A, Eshima Y, et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 2004;21:527- 38.
47. Sigmundsdottir H, Pan J, Debes GF, et al. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nat Immunol 2007;8:285-93.
48. Harada K, Isse K, Nakanuma Y. Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction. J Clin Pathol 2006;59:184-90.
49. Annacker O, Coombes JL, Malmstrom V, et al. Essential role for CD103 in the T cell-mediated regulation of experimental colitis. J Exp Med 2005;202:1051-61.
50. Husby S, Jensenius JC, Svehag SE. Passage of undegraded dietary antigen into the blood of healthy adults. Quantification, estimation of size distribution, and relation of uptake to levels of specific antibodies. Scand J Immunol 1985;22:83-92.
51. Limmer A, Ohl J, Wingender G, et al. Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance. Eur J Immunol 2005;35:2970-81.
52. Knolle PA, Limmer A. Neighborhood politics: the immunoregulatory function of organ-resident liver endothelial cells. Trends Immunol 2001;22:432-7.
53. Yang R, Liu Q, Grosfeld JL, et al. Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction. J Pediatr Surg 1994;29:1145-8.
54. Bowen DG, McCaughan GW, Bertolino P. Intrahepatic immunity: a tale of two sites? Trends Immunol 2005;26:512-7.
55. Willberg C, Barnes E, Klenerman P. HCV immunology - death and the maiden T cell. Cell Death Differ 2003;10(Suppl 1):S39-S47.
56. Fava G, Glaser S, Francis H, et al. The immunophysiology of biliary epithelium. Semin Liver Dis 2005;25:251-64.
57. Probert CS, Christ AD, Saubermann LJ, et al. Analysis of human common bile duct-associated T cells: evidence for oligoclonality, T cell clonal persistence, and epithelial cell recognition. J Immunol JID - 2985117R 1997;158:1941-8.
58. Adams DH, Afford SC. Effector mechanisms of nonsuppurative destructive cholangitis in graft-versus-host disease and allograft rejection. Semin Liver Dis 2005;25:281-97.
59. Chen XM, O'Hara SP, Nelson JB, et al. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB. J Immunol 2005;175:7447-56.
60. Karrar A, Broome U, Sodergren T, et al. Biliary epithelial cell antibodies link adaptive and innate immune responses in primary sclerosing cholangitis. Gastroenterology 2007;132:1504-14.
61. Heydtmann M, Lalor PF, Eksteen JA, et al. CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J Immunol 2005;174:1055-62.
62. Isse K, Harada K, Zen Y, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology 2005;41:506-16.
63. Efsen E, Grappone C, Defranco RM, et al. Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans. J Hepatol 2002;37:39-47.
64. Wilbanks A, Zondlo SC, Murphy K, et al. Expression cloning of the strl33/bonzo/tymstr ligand reveals elements of cc, cxc, and cx3c chemokines. J Immunol 2001;166:5145-54.
65. Boisvert J, Kunkel EJ, Campbell JJ, et al. Liver-infiltrating lymphocytes in end-stage hepatitis C virus: subsets, activation status, and chemokine receptor phenotypes. J Hepatol 2003;38:67-75.
66. Kim CH, Kunkel EJ, Boisvert J, et al. Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest 2001;107:595-601.
67. Sato T, Thorlacius H, Johnston B, et al. Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver. J Immunol 2005;174:277-83.
68. Lalor PF, Shields P, Grant A, et al. Recruitment of lymphocytes to the human liver. Immunol Cell Biol 2002;80:52-64.
69. Smith F, Golden-Mason L, Deignan T, et al. Localization of T and B lymphocytes in histologically normal adult human donor liver. Hepatogastroenterology 2003;50:1311-5.
70. Norris S, Collins C, Doherty DG, et al. Resident human hepatic lymphocytes are phenotypically different from circulating lymphocytes. J Hepatol 1998;28:84-90.
71. Khakoo SI, Carrington M. KIR and disease: a model system or system of models? Immunol Rev 2006;214:186-201.
72. Doherty DG, Norris S, Madrigal-Estebas L, et al. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol 1999;163:2314-21.
73. Ajuebor MN, Aspinall AI, Zhou F, et al. Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by preventing the apoptosis of activated CD1d-restricted NKT cells. J Immunol 2005;174:8027-37.
74. Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest 2005;115:3072-82.
75. Thomson AW, Lu L. Are dendritic cells the key to liver transplant tolerance? Immunol Today 1999;20:27-32.
76. 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. Nat Med 2000;6:1348-54.
77. Lohse AW, Knolle PA, Bilo K, et al. Antigen-presenting function and b7 expression of murine sinusoidal endothelial-cells and kupffer cells. Gastroenterology 1996;110:1175-81.
78. Wiegard C, Frenzel C, Herkel J, et al. Murine liver antigen presenting cells control suppressor activity of CD4+CD25+ regulatory T cells. Hepatology 2005;42:193-9.
79. Winau F, Hegasy G, Weiskirchen R, et al. Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity 2007;26:117-29.
80. Bowen DG, Zen M, Holz L, et al. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity. J Clin Invest 2004;114:701-12.
81. Goddard S, Youster J, Morgan E, et al. Interleukin-10 secretion differentiates dendritic cells from human liver and skin. Am J Pathol 2004;164:511-9.
82. Khanna A, Morelli AE, Zhong C, et al. Effects of liver-derived dendritic cell progenitors on Th1- and Th2-like cytokine responses in vitro and in vivo. J Immunol 2000;164:1346-54.
83. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64.
84. Wertheimer AM, Bakke A, Rosen HR. Direct enumeration and functional assessment of circulating dendritic cells in patients with liver disease. Hepatology 2004;40:335-45.
85. van der Molen RG, Sprengers D, Binda RS, et al. Functional impaitment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B. Hepatology 2004;40:738-46.
86. Uwatoku R, Suematsu M, Ezaki T, et al. Kupffer cell-mediated recruitment of rat dendritic cells to the liver: roles of N-acetylgalactosamine-specific sugar receptors. Gastroenterology 2001;121:1460-72.
87. 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.
88. Grant AJ, Goddard S, Ahmed-Choudhury J, et al. Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease. Am J Pathol 2002;160:1445-55.
89. Matsuno K, Ezaki T, Kudo S, et al. A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph [see comments]. J Exp Med 1996;183:1865-78.
90. Cremer I, Dieu-Nosjean MC, Marechal S, et al. Long-lived immature dendritic cells mediated by TRANCE-RANK interaction. Blood 2002;100:3646-55.
91. Bosma BM, Metselaar HJ, Mancham S, et al. Characterization of human liver dendritic cells in liver grafts and perfusates. Liver Transpl 2006;12:384-93.
92. Cabillic F, Rougier N, Basset C, et al. Hepatic environment elicits monocyte differentiation into a dendritic cell subset directing Th2 response. J Hepatol 2006;44:552-9.
93. Bliss SK, Bliss SP, Belting DP, et al. IL10 regulates movement of intestinale derived CD4+ T cells to the liver. J Immunol 2007;178:7974-83.
94. Erhardt A, Biburger M, Papadopoulos T, et al. IL10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice. Hepatology 2007;45:475-85.
95. Zhang M, Tang H, Guo Z, et al. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 2004;5:1124-33.
96. Saalbach A, Klein C, Sleeman J, et al. Dermal fibroblasts induce maturation of dendritic cells. J Immunol 2007;178:4966-74.
97. Lunz JG, III, Specht SM, Murase N, et al. Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity. Hepatology 2007;46:1946-59.
98. Unrig A, Banafsche R, Kremer M, et al. Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver. J Leukoc Biol 2005;77:626-33.
99. Knolle PA, Gerken G. Local control of the immune response in the liver. Immunol Rev 2000;174:21-34.
100. Abe M, Tokita D, Raimondi G, et al. Endotoxin modulates the capacity of CpG-activated liver myeloid DC to direct Th1-type responses. Eur J Immunol 2006;36:2483-93.
101. Warren A, Le Couteur DG, Fraser R, et al. T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells. Hepatology 2006;44:1182-90.
102. Lalor PF, Lai WK, Curbishley SM, et al. Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. World J Gastroenterol 2006;12:5429-39.
103. Burgdorf S, Kautz A, Bohnert V, et al. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 2007;316:612-6.
104. Berg M, Wingender G, Djandji D, et al. Cross-presentation of antigens from apoptotic tumor cells by liver sinusoidal endothelial cells leads to tumor-specific CD8+ T cell tolerance. Eur J Immunol 2006;36:2960-70.
105. Klugewitz K, Blumenthal-Barby F, Schrage A, et al. Immunomodulatory effects of the liver: deletion of activated CD4+ effector cells and suppression of IFN-gamma-producing cells after intravenous protein immunization. J Immunol JID - 2985117R 2002;169:2407-13.
106. Huang L, Soldevila G, Leeker M, et al. The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity 1994;1:741-9.
107. Mehal WZ, Juedes AE, Crispe IN. Selective retention of activated CD8+ T cells by the normal liver. J Immunol 1999;163:3202-10.
108. John B, Klein I, Crispe IN. Immune role of hepatic TLR-4 revealed by orthotopic mouse liver transplantation. Hepatology 2007;45:176-86.
109. Iwai Y, Terawaki S, Ikegawa M, et al. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 2003;198:39-50.
110. Klein I, Crispe IN. Complete differentiation of CD8+ T cells activated locally within the transplanted liver. J Exp Med 2006;203:437-47.
111. Stockinger B, Veldhoan M. Differentiation and function of Th17 T cells. Curr Opin Immunol 2007;19:281-6.
112. Wolk K, Witte E, Hoffmann U, et al. IL22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL22 in Crohn's disease. J Immunol 2007;178:5973-81.
113. Radaeva S, Sun R, Pan HN, et al. Interleukin 22 (IL22) plays a protective role in T cell-mediated murine hepatitis: IL22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 2004;39:1332-42.
114. Zenewicz LA, Yancopoulos GD, Valenzuela DM, et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 2007;27:647-59.
115. Dikopoulos N, Wegenka U, Kroger A, et al. Recently primed CD8+ T cells entering the liver induce hepatocytes to interact with naive CD8+ T cells in the mouse. Hepatology 2004;39:1256-66.
116. Salazar-Mather TP, Hamilton TA, Biton CA. A chemokine-to-cytokine- to-chemokine cascade critical in antiviral defense. J Clin Invest 2000;105:985-93.
117. Naschitz JE, Yeshurun D, Zuckerman E, et al. Massive hepatic steatosis complicating adult celiac disease: report of a case and review of the literature. Am J Gastroenterol 1987;82:1186-9.
118. Rushbrook SM, Ward SM, Unitt E, et al. Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection. J Virol 2005;79:7852-9.
119. Eksteen B, Miles A, Curbishley SM, et al. Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10. J Immunol 2006;177:593-603.
120. Curbishley SM, Eksteen B, Gladue RP, et al. CXCR3 activation promotes lymphocyte transendothelial migration across human hepatic endothelium under fluid flow. Am J Pathol 2005;167:887-99.
121. Ajuebor MN, Hogaboam CM, Le T, et al. C-C chemokine ligand 2/monocyte chemoattractant protein-1 directly inhibits NKT cell IL4 production and is hepatoprotective in T cell-mediated hepatitis in the mouse. J Immunol 2003;170:5252-9.
122. Shlomai A, Trop S, Gotsman I, et al. Immunomodulation of experimental colitis: the role of NK1.1 liver lymphocytes and surrogate antigens - bystander effect. J Pathol 2001;195:498-507.
123. Tramonti D, Andrew EM, Rhodes K, et al. Evidence for the opposing roles of different gamma delta T cell subsets in macrophage homeostasis. Eur J Immunol 2006;36:1729-38.
124. Martinez-Llordella M, Puig-Pey I, Orlando G, et al. Multiparameter immune profiling of operational tolerance in liver transplantation. Am J Transplant 2007;7:309-19.
125. Rubio-Tapia A, Murray JA. The liver in celiac disease. Hepatology 2007;46:1650-8.
126. Kingham JG, Parker DR. The association between primary biliary cirrhosis and coeliac disease: a study of relative prevalences. Gut 1998;42:120-2.
127. Bardella MT, Vecchi M, Conte D, et al. Chronic unexplained hypertransaminasemia may be caused by occult celiac disease. Hepatology 1999;29:654-7.
128. Volta U, Rodrigo L, Granito A, et al. Celiac disease in autoimmune cholestatic liver disorders. Am J Gastroenterol 2002;97:2609-13.
129. Lawson A, West J, Aithal GP, et al. Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association. Aliment Pharmacol Ther 2005;21:401-5.
130. Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610-5.
131. Chapman RW. Aetiology and natural history of primary sclerosing cholangitis - a decade of progress? Gut 1991;32:1433-5.
132. Rabinovitz M, Gavaler JS, Schade RR, et al. Does primary sclerosing cholangitis occurring in association with inflammatory bowel disease differ from that occurring in the absence of inflammatory bowel disease? A study of sixty-six subjects. Hepatology 1990;11:7-11.
133. Loftus EV Jr, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005;54:91-6.
134. Helzberg JH, Petersen JM, Boyer JL. Improved survival with primary sclerosing cholangitis. A review of clinicopathologic features and comparison of symptomatic and asymptomatic patients. Gastroenterology 1987;92:1869-75.
135. Takikawa H, Manabe T. Primary sclerosing cholangitis in Japan - analysis of 192 cases. J Gastroenterol 1997;32:134-7.
136. Donlin LT, Danzl NM, Wanjalla C, et al. Deficiency in expression of the signaling protein Sin/Efs leads to T-lymphocyte activation and mucosal inflammation. Mol Cell Biol 2005;25:11035-46.
137. Matsumoto S, Okabe Y, Setoyama H, et al. Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain. Gut 1998;43:71-8.
138. Grant AJ, Lalor PF, Salmi M, et al. Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease. Lancet 2002;359:150-7.
139. Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 1998;42:387-91.
140. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology 2002;123:714-8.
141. Salmi M, Andrew DP, Butcher EC, et al. Dual binding capacity of mucosal immunoblasts to mucosal and synovial endothelium in humans: dissection of the molecular mechanisms. J Exp Med 1995;181:137-49.
142. Brandtzaeg P. Review article: Homing of mucosal immune cells - a possible connection between intestinal and articular inflammation. Aliment Pharmacol Ther 1997;11(Suppl 3):24-37.
143. Gualdi R, Bossard P, Zheng M, et al. Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 1996;10:1670-82.
144. Yoshida H, Kawamoto H, Santee SM, et al. Expression of alpha(4)beta(7) integrin defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells. J Immunol 2001;167:2511-21.
145. Salmi M, Rajala P, Jalkanen S. Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion. J Clin Invest 1997;99:2165-72.
146. Juillerat P, Mottet C, Froehlich F, et al. Extraintestinal manifestations of Crohn's disease. Digestion 2005;71:31-6.
147. Hillan KJ, Hagler KE, MacSween RN, et al. Expression of the mucosal vascular addressin, MAdCAM-1. in inflammatory liver disease. Liver 1999;19:509-18.
148. Grant AJ, Lalor PF, Hubscher SG, et al. MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology 2001;33:1065-72.
149. Lalor PF, Edwards S, McNab G, et al. Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells. J Immunol 2002;169:983-92.
150. Salmi M, Kalimo K, Jalkanen S. Induction and function of vascular adhesion protein-1 at sites of inflammation. J Exp Med 1993;178:2255-60.
151. Oertelt S, Ridgway WM, Ansari AA, et al. Murine models of primary biliary cirrhosis: Comparisons and contrasts. Hepatol Res 2007;37(Suppl 3):S365-9.
152. Wakabayashi K, Lian ZX, Moritoki Y, et al. IL2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Hepatology 2006;44:1240-9.
153. Murai M, Yoneyama H, Ezaki T, et al. Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat Immunol 2003;4:154-60.
154. Petrovic A, Alpdogan O, Willis LM, et al. LPAM (alpha 4 beta 7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood 2004;103:1542-7.
155. Ward SM, Jonsson JR, Sierra S, et al. Virus-specific CD8+ T lymphocytes within the normal human liver. Eur J Immunol 2004;34:1526-31.
156. Polakos NK, Klein I, Richter MV, et al. Early intrahepatic accumulation of CD8+ T cells provides a source of effectors for nonhepatic immune responses. J Immunol 2007;179:201-10.
157. Pope C, Kim SK, Marzo A, et al. Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection. J Immunol 2001;166:3402-9.
158. Klonowski KD, Williams KJ, Marzo AL, et al. Dynamics of blood-borne CD8 memory T cell migration in vivo. Immunity 2004;20:551-62.
159. Uhlig HH, Powrie F. The role of mucosal T lymphocytes in regulating intestinal inflammation. Springer Semin Immunopathol 2005;27:167-80.
160. Bliss SK, Alcaraz A, Appleton JA. IL10 prevents liver necrosis during murine infection with Trichinella spiralis. J Immunol 2003;171:3142-7.