Viral Hepatitis

You have full text access to this OnlineOpen article

CCR5 deficiency exacerbates T-cell–mediated hepatitis in mice†

  1. Christophe Moreno1,2,‡,§,*,
  2. Thierry Gustot1,2,
  3. Charles Nicaise2,
  4. Eric Quertinmont2,
  5. Nathalie Nagy3,
  6. Marc Parmentier4,
  7. Olivier Le Moine1,2,
  8. Jacques Devière1,2,
  9. Hubert Louis1,2

Article first published online: 20 SEP 2005

DOI: 10.1002/hep.20865

Issue

Hepatology

Hepatology

Volume 42, Issue 4, pages 854–862, October 2005

Additional Information

How to Cite

Moreno, C., Gustot, T., Nicaise, C., Quertinmont, E., Nagy, N., Parmentier, M., Le Moine, O., Devière, J. and Louis, H. (2005), CCR5 deficiency exacerbates T-cell–mediated hepatitis in mice. Hepatology, 42: 854–862. doi: 10.1002/hep.20865

Author Information

  1. 1

    Division of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium

  2. 2

    Laboratory of Experimental Gastroenterology, Free University of Brussels, Brussels, Belgium

  3. 3

    Division of Pathology, Erasme Hospital, Brussels, Belgium

  4. 4

    Institute of Interdisciplinary Research, Free University of Brussels, Brussels, Belgium

  1. ‡

    fax: (32) 2-555-46-97

  2. §

    C.M. is a research fellow of the Fondation Erasme.

*Division of Gastroenterology and Hepato-Pancreatology, Erasme University Hospital, 808, route de Lennik, B 1070 Brussels, Belgium

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 20 SEP 2005
  2. Article first published online: 20 SEP 2005
  3. Manuscript Accepted: 18 JUL 2005
  4. Manuscript Received: 7 FEB 2005

Funded by

  • Fondation Erasme
  • Fonds National de la Recherche Scientifique of Belgium

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (316K)

References

  • 1
    Tilg H, Dielh AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000; 343: 1467–1476.
  • 2
    Di Bisceglie AM, McHutchinson J, Rice CM. New therapeutic strategies for hepatitis C. HEPATOLOGY 2002; 35: 224–231.
    Direct Link:
  • 3
    Valiante NM, D'Andrea A, Crotta S, Lechner F, Klenerman P, Nuti S, et al. Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C. Immunol Rev 2000; 174: 77–89.
    Direct Link:
  • 4
    Mabee CL, Thiele DL. Mechanisms of autoimmune liver disease. Clin Liver Dis 2000; 4: 431–445.
  • 5
    Tiegs G, Hentschel J, Wendel A. A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest 1992; 90: 196–203.
  • 6
    Mizuhara H, O'Neill E, Seki N, Ogawa T, Kusunoki C, Otsuka K, et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med 1994; 179: 1529–1537.
  • 7
    Küsters S, Gantner F, Künstle G, Tiegs G. Interferon gamma plays a critical role in T cell-dependent liver injury in mice initiated by concanavalin A. Gastroenterology 1996; 111: 162–171.
  • 8
    Kaneko Y, Harada M, Kawano T, Yamashita M, Shibata Y, Gejyo F, et al. Augmentation of Vα14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis. J Exp Med 2000; 191: 105–114.
  • 9
    Nicoletti F, DiMarco R, Zaccone P, Salvaggi A, Magro G, Bendtzen K, et al. Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-γ-dependent mechanism. HEPATOLOGY 2000; 32: 728–733.
    Direct Link:
  • 10
    Louis H, Le Moine A, Flamand V, Nagy N, Quertinmont E, Paulart F, et al. Critical role of interleukin 5 and eosinophils in concanavalin A-induced hepatitis in mice. Gastroenterology 2002; 122: 2001–2010.
  • 11
    Schumann J, Wolf D, Pahl A, Brune K, Papadopoulos T, van Rooijen N, et al. Importance of Kupffer cells for T-cell-dependent liver injury in mice. Am J Pathol 2000; 157: 1671–1683.
  • 12
    Bonder CS, Ajuebor MN, Zbytnuik LD, Kubes P, Swain MG. Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis. J Immunol 2004; 172: 45–53.
  • 13
    Simpson KJ, Henderson NC, Bone-Larson CL, Lukacs NW, Hogaboam CM, Kunkel SL. Chemokines in the pathogenesis of liver disease: so many players with poorly defined roles. Clin Sci 2003; 104: 47–63.
  • 14
    Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 1996; 35: 3362–3367.
  • 15
    Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382: 722–725.
  • 16
    Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol 2001; 2: 102–107.
  • 17
    Mack M, Cihak J, Simonis C, Luckow B, Proudfoot AEI, Plachy J, et al. Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J Immunol 2001; 166: 4697–4704.
  • 18
    Shields PL, Morland CM, Salmon M, Qin S, Hubscher SG, Adams DH. Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver. J Immunol 1999; 163: 6236–6243.
  • 19
    Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, et al. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. HEPATOLOGY 2003; 38: 1468–1476.
  • 20
    Eri R, Jonsson JR, Pandeya N, Purdie DM, Clouston AD, Martin N, et al. CCR5-Delta32 mutation is strongly associated with primary sclerosing cholangitis. Genes Immun 2004; 5: 444–450.
  • 21
    Moench C, Uhrig A, Lohse AW, Otto G. CC chemokine receptor 5delta32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation. Liver Transpl 2004; 10: 434–439.
    Direct Link:
  • 22
    Stordeur P, Poulin LF, Graciun L, Zhou L, Schandene L, de Lavareille A, et al. Cytokine quantification by real-time PCR. J Immunol Methods 2002; 259: 55–64.
  • 23
    Do H, Healey JF, Waller EK, Lollar P. Expression of factor VIII by murine liver sinusoidal endothelial cells. J Biol Chem 1999; 274: 19587–19592.
  • 24
    Leifeld L, Dumoulin FL, Purr I, Janberg K, Trautwein C, Wolff M, et al. Early up-regulation of chemokine expression in fulminant hepatic failure. J Pathol 2003; 199: 335–344.
    Direct Link:
  • 25
    Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol 2002; 283: R7–R28.
  • 26
    Gao JL, Wynn TA, Chang Y, Lee EJ, Broxmeyer HE, Cooper S, et al. Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 1997; 185: 1959–1968.
  • 27
    Kurihara T, Warr G, Loy J, Bravo R. Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med 1997; 186: 1757–1762.
  • 28
    Zhou Y, Kurihara T, Ryseck RP, Yang Y, Ryan C, Loy J, et al. Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J Immunol 1998; 160: 4018–4025.
  • 29
    Dawson TC, Beck MA, Kuziel WA, Henderson F, Maeda N. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am J Pathol 2000; 156: 1951–1959.
  • 30
    Welniak LA, Wang Zhao, Sun K, Kuziel W, Anver MR, Blazar BR, et al. An absence of CCR5 on donor cells results in acceleration of acute graft-vs-host disease. Exp Hematol 2004; 32: 318–324.
  • 31
    Wysocki CA, Burkett SB, Panoskaltsis-Mortari A, Kirby SL, Luster AD, McKinnon K, et al. Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning. J Immunol 2004; 173: 845–854.
  • 32
    Algood HM, Flynn JL. CCR5-deficient mice control Mycobacterium tuberculosis infection despite increased pulmonary lymphocytic infiltration. J Immunol 2004; 173: 3287–3296.
  • 33
    Toyabe S, Seki S, Iiai T, Takeda K, Shirai K, Watanabe H, et al. Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic injury in mice. J Immunol 1997; 159: 1537–1542.
  • 34
    Jaruga B, Hong F, Sun R, Radaeva S, Gao B. Crucial role of IL-4/STAT6 in T cell-mediated hepatitis: up-regulating eotaxins and IL-5 and recruiting leukocytes. J Immunol 2003; 171: 3233–3244.
  • 35
    Ajuebor MN, Hogaboam CM, Le T, Proudfoot AEI, Swain MG. CCL3/MIP-1α is pro-inflammatory in murine T cell-mediated hepatitis by recruiting CCR1-expressing CD4+ T cells to the liver. Eur J Immunol 2004; 34: 2907–2918.
    Direct Link:
  • 36
    Cartier L, Dubois-Dauphin M, Hartley O, Irminger-Finger I, Krause KH. Chemokine-induced cell death in CCR5-expressing neuroblastoma cells. J Neuroimmunol 2003; 145: 27–39.
  • 37
    Algeciras-Schimnich A, Vlahakis SR, Villasis-Keever A, Gomez T, Heppelmann CJ, Bou G, et al. CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells. AIDS 2002; 16: 1467–1478.
  • 38
    Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci U S A 2000; 97: 5498–5503.
  • 39
    Itoh Y, Morita A, Nishioji K, Fujii H, Nakamura H, Kirishima T, et al. Time course profile and cell-type-specific production of monokine induced by interferon-gamma in concanavalin A-induced hepatic injury in mice: comparative study with interferon-inducible protein-10. Scand J Gastroenterol 2001; 36: 1344–1351.
  • 40
    Maus UA, Wellmann S, Hampl C, Kuziel WA, Srivastava M, Mack M, et al. CCR2 positive monocytes recruited to inflamed lungs downregulate local CCL2 chemokine levels. Am J Physiol Lung Cell Mol Physiol 2005; 288: L350–L358.
  • 41
    Yanaba K, Mukaida N, Matsushima K, Murphy PM, Takehara K, Sato S. Role of C-C chemokine receptors 1 and 5 and CCL3/macrophage inflammatory protein-1α in the cutaneous Arthus reaction: possible attenuation of their inhibitory effects by compensatory chemokine production. Eur J Immunol 2004; 34: 3553–3561.
    Direct Link:
  • 42
    Glass WG, Hickey MJ, Hardison JL, Liu MT, Manning JE, Lane TE. Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis. J Immunol 2004; 172: 4018–4025.
  • 43
    Promrat A, McDermott DH, Gonzales CM, Kleiner DE, Koziol DE, Lessie M, et al. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology 2003; 124: 352–360.
View Full Article (HTML) Get PDF (316K)