Seminars in Immunopathology

, 31:399 | Cite as

Liver architecture, cell function, and disease

  • Hiromi Ishibashi
  • Minoru Nakamura
  • Atsumasa Komori
  • Kiyoshi Migita
  • Shinji Shimoda


The liver is an organ consisting of the largest reticulo-endothelial cell network in the body and playing an important role in host defense against invading microorganisms. The organ is comprised of parenchymal cells and many different types of non-parenchymal cells, all of which play a significant role. Even biliary epithelial cells are not only the target in autoimmune liver diseases but also have central role in orchestrating several immune cells involved in both innate and acquired immunity. Tissue damage caused by various agents results in inflammation, necrosis, fibrosis, and, eventually, distortion of normal hepatic architecture, cirrhosis, and functional deterioration.


Innate immunity Kupffer cells Cytokine Chemokine Toll-like receptor 



autoimmune hepatitis


activated liver myofibroblasts


antigen-presenting cell


biliary epithelial cells


conventional DC


common lymphatic endothelial and vascular endothelial receptor-1


chronic non-suppurative destructive cholangitis


damage-associated molecular pattern


dendritic cells


epithelial neutrophil chemoattractant-78


growth-related oncoprotein


Hepatic stellate cells


intercellular adhesion molecule-1






hepatocellular carcinoma


jun N-terminal kinase




liver-infiltrated mononuclear cells


liver sinusoidal endothelial cells


myelin basic protein




monocyte chemotactic protein-1


non-alcoholic steatohepatitis


nucleotide-binding oligomerization domain


pathogen-associated molecular patterns


primary biliary cirrhosis


plasmatoid DC


pattern-recognition receptors


primary sclerosing cholangitis


reactive oxygen species


toll-like receptor


tumor necrosis factor


vascular cell adhesion molecule-1


  1. 1.
    Afford SC, Ahmed-Choudhury J, Randhawa S, Russell C, Youster J, Crosby HA, Eliopoulos A, Hubscher SG, Young LS, Adams DH (2001) CD40 activation-induced, Fas-dependent apoptosis and NF-kappaB/AP-1 signaling in human intrahepatic biliary epithelial cells. FASEB J 15:2345–2354. doi: 10.1096/fj.01-0088com S28CrossRefPubMedGoogle Scholar
  2. 2.
    Berg PA, Klein R, Rocken M (1997) Cytokines in primary biliary cirrhosis. Semin Liver Dis 17:115–123. doi: 10.1055/s-2007-1007189 S7CrossRefPubMedGoogle Scholar
  3. 3.
    Bettelli E, Oukka M, Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350. doi: 10.1038/ni0407-345 S6CrossRefPubMedGoogle Scholar
  4. 4.
    Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621. doi: 10.1056/NEJMra052723 S15CrossRefPubMedGoogle Scholar
  5. 5.
    Chen XM, O’Hara SP, Nelson JB, Splinter PL, Small AJ, Tietz PS, Limper AH, LaRusso NF (2005) Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappa B. J Immunol 175:7447–7756 S23PubMedGoogle Scholar
  6. 6.
    Diehl L, Schurich A, Grochtmann R, Hegenbarth S, Chen L, Knolle PA (2008) Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+T cell tolerance. Hepatology 47:296–305. doi: 10.1002/hep.21965 K4CrossRefPubMedGoogle Scholar
  7. 7.
    Ge X, Uzunel M, Ericzon B-G, Sumitran-Holgersson S (2005) Biliary epithelial cell antibodies induce expression of toll-like receptor 2 and 3: a mechanism for post-liver transplantation cholangitis. Liver Transpl 11:911–921. doi: 10.1002/lt.20420 N23CrossRefPubMedGoogle Scholar
  8. 8.
    Gregory SH, Wing EJ (2002) Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections. J Leukoc Biol 72:239–248 M2PubMedGoogle Scholar
  9. 9.
    Gumucio JJ (1989) Hepatocyte heterogeneity: the coming of age from the description of a biological curiosity to a partial understanding of its physiological meaning and regulation. Hepatology 9:154–160. doi: 10.1002/hep.1840090124 I3CrossRefPubMedGoogle Scholar
  10. 10.
    Gumucio JJ, Berkovitz CM, Webster ST, Thornton AJ (1996) Structural and functional organization of the liver. In: Kaplowitz N (ed) Liver and biliary diseases, 2nd edn. Williams & Wilkins, Baltimore, pp 3–19 [I1]Google Scholar
  11. 11.
    Guo J, Loke J, Zheng F, Hong F, Yea S, Fukata M et al (2009) Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of toll-like receptor 4 to hepatic stellate cell responses. Hepatology 49:960–968. doi: 10.1002/hep.22697 N11CrossRefPubMedGoogle Scholar
  12. 12.
    Gustot T, Lemmers A, Moreno C, Nagy N, Quertinmont E, Nicaise C et al (2006) Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver. Hepatology 43:989–1000. doi: 10.1002/hep.21138 N9CrossRefPubMedGoogle Scholar
  13. 13.
    Harada K, Isse K, Nakanuma Y (2006) Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction. J Clin Pathol 59:184–190. doi: 10.1136/jcp.2004.023507 S1CrossRefPubMedGoogle Scholar
  14. 14.
    Harada K, Ohira S, Isse K, Ozaki S, Zen Y, Sato Y et al (2003) Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells. Lab Invest 83:1657–1667. doi: 10.1097/01.LAB.0000097190.56734.FE N16CrossRefPubMedGoogle Scholar
  15. 15.
    Harada K, Ozaki S, Gershwin ME, Nakanuma Y (1997) Enhanced apoptosis relates to bile duct loss in primary biliary cirrhosis. Hepatology 26:1399–1405. doi: 10.1002/hep.510260604 S5CrossRefPubMedGoogle Scholar
  16. 16.
    Harada K, Van de Water J, Leung PS, Coppel RL, Ansari A, Nakanuma Y, Gershwin ME (1997) In situ nucleic acid hybridization of cytokines in primary biliary cirrhosis: predominance of the Th1 subset. Hepatology 25:791–796. doi: 10.1002/hep.510250402 S10CrossRefPubMedGoogle Scholar
  17. 17.
    Hendriks HF, Verhoofstad WA, Brouwer A, de Leeuw AM, Knook DL (1985) Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver. Exp Cell Res 160:138–149. doi: 10.1016/0014-4827(85)90243-5 I5CrossRefPubMedGoogle Scholar
  18. 18.
    Holt AP, Haughton EL, Lalor PF, Flier A, Buckley CD, Adams DH (2008) Liver myofibroblasts regulate infiltration and positioning of lymphocytes in human liver. Gastroenterology 136:705–714. doi: 10.1053/j.gastro.2008.10.020 K6CrossRefPubMedGoogle Scholar
  19. 19.
    Hritz I, Velayudham A, Dolganiuc A, Kodys K, Mandrekar P, Kurt-Jones E et al (2008) Bone Marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion. Hepatology 48:1342–1347. doi: 10.1002/hep.22557 N5CrossRefPubMedGoogle Scholar
  20. 20.
    Isse K, Harada K, Sato Y, Nakanuma Y (2006) Characterization of biliary intra-epithelial lymphocytes at different anatomical levels of intrahepatic bile ducts under normal and pathological conditions: numbers of CD4+CD28− intra-epithelial lymphocytes are increased in primary biliary cirrhosis. Pathol Int 56:17–24 S11PubMedGoogle Scholar
  21. 21.
    Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216. doi: 10.1146/annurev.immunol.20.083001.084359 M8CrossRefPubMedGoogle Scholar
  22. 22.
    Kamihira T, Shimoda S, Harada K, Kawano A, Handa M, Baba E, Tsuneyama K, Nakamura M, Ishibashi H, Nakanuma Y, Gershwin ME, Harada M (2003) Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis. Gastroenterology 125:1379–1387. doi: 10.1016/j.gastro.2003.07.013 S12CrossRefPubMedGoogle Scholar
  23. 23.
    Kamihira T, Shimoda S, Nakamura M, Yokoyama T, Takii Y, Kawano A, Handa M, Ishibashi H, Gershwin ME, Harada M (2005) Biliary epithelial cells regulate autoreactive T cells: implications for biliary-specific diseases. Hepatology 41:151–159. doi: 10.1002/hep.20494 S30CrossRefPubMedGoogle Scholar
  24. 24.
    Karrar A, Broome U, Sodergren T, Jaksch M, Bergquist A, Bjornstedt M et al (2007) Biliary epithelial cell antibodies link adaptive and innate immune responses in primary sclerosing cholangitis. Gastroenterology 132:1504–1514. doi: 10.1053/j.gastro.2007.01.039 N22CrossRefPubMedGoogle Scholar
  25. 25.
    Kikuchi K, Lian Z-X, Yang G-X, Ansari AA, Ikehara S, Kaplan M et al (2005) Bacterial CpG induces hyper IgM production in CD27+ memory B cells in primary biliary cirrhosis. Gastroenterology 128:304–312. doi: 10.1053/j.gastro.2004.11.005 N20CrossRefPubMedGoogle Scholar
  26. 26.
    Kmieć Z (2001) Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol 161:III–XIII, 1–151. M16Google Scholar
  27. 27.
    Komori A, Nakamura M, Fujiwara S, Yano K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H (2007) Human intrahepatic biliary epithelial cells as a possible modulator of hepatic regeneration: potential role of biliary epithelial cell for hepatic remodeling in vivo. Hepatol Res 37(Suppl 3):S438–S443. doi: 10.1111/j.1872-034X.2007.00237.x K8CrossRefPubMedGoogle Scholar
  28. 28.
    Krams SM, Van de Water J, Coppel RL, Esquivel C, Roberts J, Ansari A, Gershwin ME (1990) Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis. Hepatology 12:306–313. doi: 10.1002/hep.1840120219 S3CrossRefPubMedGoogle Scholar
  29. 29.
    Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, Yee H, Zender L, Lowe SW (2008) Senescence of activated stellate cells limits liver fibrosis. Cell 134:657–667. doi: 10.1016/j.cell.2008.06.049 K7CrossRefPubMedGoogle Scholar
  30. 30.
    Krutzik SR, Sieling PA, Modlin RL (2001) The role of Toll-like receptors in host defense against microbial infection. Curr Opin Immunol 13:104–108. doi: 10.1016/S0952-7915(00)00189-8 S20CrossRefPubMedGoogle Scholar
  31. 31.
    Kunkel SL, Godessart N (2002) Chemokines in autoimmunity: from pathology to therapeutics. Autoimmun Rev 1:313–320. doi: 10.1016/S1568-9972(02)00085-X S18CrossRefPubMedGoogle Scholar
  32. 32.
    Lan RY, Cheng C, Lian ZX, Tsuneyama K, Yang GX, Moritoki Y, Chuang YH, Nakamura T, Saito S, Shimoda S, Tanaka A, Bowlus CL, Takano Y, Ansari AA, Coppel RL, Gershwin ME (2006) Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology 43:729–737. doi: 10.1002/hep.21123 S14CrossRefPubMedGoogle Scholar
  33. 33.
    Lang KS, Georgiev P, Recher M, Navarini AA, Bergthaler A, Heikenwalder M et al (2006) Immunoprivileged status of the liver is controlled by toll-like receptor 3 signaling. J Clin Invest 116:2456–2463. doi: 10.1172/JCI28349 N12CrossRefPubMedGoogle Scholar
  34. 34.
    Lee MS, Kim Y-J (2007) Pattern-recognition receptor signaling initiated from extracellular, membrane, and cytoplasmic space. Mol Cells 23:1–10 N2PubMedGoogle Scholar
  35. 35.
    Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–983. doi: 10.1016/S0092-8674(00)80172-5 S19CrossRefPubMedGoogle Scholar
  36. 36.
    Lenschow DJ, Herold KC, Rhee L, Patel B, Koons A, Qin HY, Fuchs E, Singh B, Thompson CB, Bluestone JA (1996) CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity 5:285–293. doi: 10.1016/S1074-7613(00)80323-4 S13CrossRefPubMedGoogle Scholar
  37. 37.
    Lohr HF, Schlaak JF, Gerken G, Fleischer B, Dienes HP, Meyer zum Büschenfelde KH (1994) Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. Liver 14:161–166 S9PubMedGoogle Scholar
  38. 38.
    Lűth S, Huber S, Schramm C, Buch T, Zander S, Stadelmann C, Brűk W, Wraith DC, Herkel J, Lohse AW (2008) Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune necroinflammation by antigen-specific Tregs. J Clin Invest 118:3403–3410 K2PubMedGoogle Scholar
  39. 39.
    MacPhee PJ, Schmidt EE, Groom AC (1992) Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy. Am J Physiol 263:G17–G23 M1PubMedGoogle Scholar
  40. 40.
    Mao TK, Lian Z-X, Selmi C, Ichiki Y, Ashwood P, Ansari AA et al (2005) Hepatology 42:802–808. doi: 10.1002/hep.20859 N19CrossRefPubMedGoogle Scholar
  41. 41.
    Martinez OM, Villanueva JC, Gershwin ME, Krams SM (1995) Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis. Hepatology 21:113–119 S8PubMedGoogle Scholar
  42. 42.
    Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442:39–44. doi: 10.1038/nature04946 M10CrossRefPubMedGoogle Scholar
  43. 43.
    Mora JR, von Andrian UH (2006) T-cell homing specificity and plasticity: new concepts and future challenges. Trends Immunol 27:235–243. doi: 10.1016/ S17CrossRefPubMedGoogle Scholar
  44. 44.
    Moritoki Y, Lian ZX, Wulff H, Yang G-X, Chuang Y-H, Lan RY et al (2007) AMA production in primary biliary cirrhosis is promoted by the TLR9 ligand CpG and suppressed by potassium channel blockers. Hepatology 45:314–322. doi: 10.1002/hep.21522 CrossRefPubMedGoogle Scholar
  45. 45.
    Mrass P, Weninger W (2006) Immune cell migration as a means to control immune privilege: lessons from the CNS and tumors. Immunol Rev 213:195–212. doi: 10.1111/j.1600-065X.2006.00433.x S16, N21CrossRefPubMedGoogle Scholar
  46. 46.
    Naito M, Hasegawa G, Takahashi K (1997) Development, differentiation, and maturation of Kupffer cells. Microsc Res Tech 39:350–364. doi: 10.1002/(SICI)1097-0029(19971115)39:4<350::AID-JEMT5>3.0.CO;2-L M4CrossRefPubMedGoogle Scholar
  47. 47.
    Nakamura M, Funami K, Komori A, Yokoyama T, Aiba Y, Araki A et al (2008) Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers. Hepatol Int 2:222–230. doi: 10.1007/s12072-008-9055-4 N15CrossRefPubMedGoogle Scholar
  48. 48.
    Nakanuma Y, Kono N (1991) Expression of HLA-DR antigens on interlobular bile ducts in primary biliary cirrhosis and other hepatobiliary diseases: an immunohistochemical study. Hum Pathol 22:431–436. doi: 10.1016/0046-8177(91)90127-B S27CrossRefPubMedGoogle Scholar
  49. 49.
    Otte JM, Cario E, Podolsky DK (2004) Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology 126:1054–1070. doi: 10.1053/j.gastro.2004.01.007 N6CrossRefPubMedGoogle Scholar
  50. 50.
    Papadimitraki ED, Bertsias GK, Boumpas DT (2007) Toll like receptors and autoimmunity: a critical appraisal. J Autoimmun 29:310–318 N3PubMedGoogle Scholar
  51. 51.
    Pariesak A, Schafer C, Schutz T, Bode JC, Bode C (2000) Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcoholic abuse in different stages of alcohol-induced liver disease. J Hepatol 32:742–747. doi: 10.1016/S0168-8278(00)80242-1 N24CrossRefGoogle Scholar
  52. 52.
    Racanelli V, Rehermann B (2006) The liver as an immunological organ. Hepatology 43:S54–S62. doi: 10.1002/hep.21060 M15CrossRefPubMedGoogle Scholar
  53. 53.
    Rappaport AM, Borowy ZJ, Lougheed WM, Lotto WN (1954) Subdivision of hexagonal liver lobules into a structural and functional unit; role in hepatic physiology and pathology. Anat Rec 119:11–33. doi: 10.1002/ar.1091190103 I2CrossRefPubMedGoogle Scholar
  54. 54.
    Rivera CA, Adegboyega P, van Rooijen N, Tagalicud A, Allman M, Wallace M (2007) Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J Hepatol 47:571–579. doi: 10.1016/j.jhep. 2007.04.019 N8CrossRefPubMedGoogle Scholar
  55. 55.
    Roland CR, Walp L, Stack RM, Flye MW (1994) Outcome of Kupffer cell antigen presentation to a cloned murine Th1 lymphocyte depends on the inducibility of nitric oxide synthase by IFN-gamma. J Immunol 153:5453–5464 M14PubMedGoogle Scholar
  56. 56.
    Schwabe RF, Seki E, Brenner DA (2006) Toll-like receptor signaling in the liver. Gastroenterology 130:1886–1900. doi: 10.1053/j.gastro.2006.01.038 N1CrossRefPubMedGoogle Scholar
  57. 57.
    Seki E, Brenner DA (2008) Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 48:322–335. doi: 10.1002/hep.22306 N4CrossRefPubMedGoogle Scholar
  58. 58.
    Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA et al (2007) TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 13:1324–1332. doi: 10.1038/nm1663 N7CrossRefPubMedGoogle Scholar
  59. 59.
    Shetty S, Lalor PF, Adams DH (2008) Lymphocyte recruitment to the liver: molecular insights into the pathogenesis of liver injury and hepatitis. Toxicology 254:136–146. doi: 10.1016/j.tox.2008.08.003 K3CrossRefPubMedGoogle Scholar
  60. 60.
    Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A, Maehara Y, Tsuneyama K, Nakamura M, Komori A, Migita K, Nakanuma Y, Ishibashi H, Selmi C, Gershwin ME (2008) Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells. Hepatology 47:958–965. doi: 10.1002/hep.22102 S31CrossRefPubMedGoogle Scholar
  61. 61.
    Tacke F, Luedde T, Trautwein C (2009) Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol 36:4–12. doi: 10.1007/s12016-008-8091-0 M17CrossRefPubMedGoogle Scholar
  62. 62.
    Takii Y, Nakamura M, Ito M, Yokoyama T, Komori A, Shimizu-Yoshida Y, Nakao R, Kusumoto K, Nagaoka S, Yano K, Abiru S, Ueki T, Matsumoto T, Daikoku M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Nakashima M, Harada M, Ishibashi H (2005) Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis. Lab Invest 85:908–920. doi: 10.1038/labinvest.3700285 N13, S25CrossRefPubMedGoogle Scholar
  63. 63.
    Tsuneyama K, Harada K, Yasoshima M, Kaji K, Gershwin ME, Nakanuma Y (1998) Expression of co-stimulatory factor B7–2 on the intrahepatic bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis: an immunohistochemical study. J Pathol 186:126–130. doi: 10.1002/(SICI)1096-9896(1998100)186:2<126::AID-PATH167>3.0.CO;2-1 S29CrossRefPubMedGoogle Scholar
  64. 64.
    Wang AP, Migita K, Ito M, Takii Y, Daikoku M, Yokoyama T, Komori A, Nakamura M, Yatsuhashi H, Ishibashi H (2005) Hepatic expression of toll-like receptor 4 in primary biliary cirrhosis. J Autoimmun 25:85–91. doi: 10.1016/j.jaut.2005.05.003 N14, S26CrossRefPubMedGoogle Scholar
  65. 65.
    Watanabe A, Hashmi A, Gomes DA, Town T, Badou A, Flavell RA et al (2007) Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9. Hepatology 46:1509–1518. doi: 10.1002/hep.21867 N10CrossRefPubMedGoogle Scholar
  66. 66.
    Wick MJ, Leithäuser F, Reimann J (2002) The hepatic immune system. Crit Rev Immunol 22:47–103 M3PubMedGoogle Scholar
  67. 67.
    Wiegaed C, Wolint P, Frenzel C, Cheruti U, Schmitt E, Oxenius A, Lohse AW, Herkel J (2007) Defective T helper response of hepatocyte-stimulated CD4 T cells impairs antiviral CD8 response and viral clearance. Gastroenterology 133:2010–2018. doi: 10.1053/j.gastro.2007.09.007 K1CrossRefGoogle Scholar
  68. 68.
    Winau F, Quack C, Darmoise A, Kaufmann SHE (2008) Starring stellate cells in liver immunology. Curr Opin Immunol 20:68–74. doi: 10.1016/j.coi.2007.10.006 K5CrossRefPubMedGoogle Scholar
  69. 69.
    Wisse E, Braet F, Luo D, De Zanger R, Jans D, Crabbé E, Vermoesen A (1996) Structure and function of sinusoidal lining cells in the liver. Toxicol Pathol 24:100–111. doi: 10.1177/019262339602400114 I4CrossRefPubMedGoogle Scholar
  70. 70.
    van den Oord JJ, Fevery J, de Groote J, Desmet VJ (1984) Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis. Liver 4:264–274 S2PubMedGoogle Scholar
  71. 71.
    Yamada G, Hyodo I, Tobe K, Mizuno M, Nishihara T, Kobayashi T, Nagashima H (1986) Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis. Hepatology 6:385–391. doi: 10.1002/hep.1840060309 S4CrossRefPubMedGoogle Scholar
  72. 72.
    Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira T, Shimoda S, Mori T, Fujiwara S, Koyabu M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H (2006) Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways. Liver Int 26:467–476. doi: 10.1111/j.1478-3231.2006.01254.x N17, S24CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hiromi Ishibashi
    • 1
  • Minoru Nakamura
    • 1
  • Atsumasa Komori
    • 1
  • Kiyoshi Migita
    • 1
  • Shinji Shimoda
    • 2
  1. 1.Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Kyushu University Graduate School of Medical SciencesNagasakiJapan

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