CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice

Christophe Moreno, Thierry Gustot, Charles Nicaise, Eric Quertinmont, Nathalie Nagy, Marc Parmentier, Olivier Le Moine, Jacques Devière, Hubert Louis

Research output: Contribution to journalArticlepeer-review


Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A-induced liver injury. Serum levels of CCR5 ligands and their hepatic transcript levels were significantly increased after Con A injection, whereas CCR5+ liver mononuclear cells were recruited to the liver. CCR5-deficient (CCR5-/-) mice disclosed increased mortality and liver injury following Con A administration compared with wild-type mice. CCR5-/- mice also exhibited increased production of interleukin 4, tumor necrosis factor alpha, CCL3, CCL4, and CCL5, and a prominent liver mononuclear cell infiltrate, among which many cells were CCR1+. In vivo neutralization of CCR5 ligands in CCR5-/- mice afforded a protection against hepatitis only when CCL5 was neutralized. In conclusion, CCR5 deficiency exacerbates T-cell-mediated hepatitis, and leads to increased levels of CCR5 ligands and a more pronounced liver mononuclear infiltrate, suggesting that CCR5 expression can modulate severity of immuno-mediated liver injury.
Original languageEnglish
Pages (from-to)854-62
Number of pages9
JournalHepatology (Baltimore, Md.)
Issue number4
Publication statusPublished - Oct 2005


  • Animals
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines, CC
  • Concanavalin A
  • Drug-Induced Liver Injury
  • Female
  • Interferon-gamma
  • Interleukin-4
  • Ligands
  • Liver
  • Macrophage Inflammatory Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, CCR5
  • Severity of Illness Index
  • T-Lymphocytes
  • Tumor Necrosis Factor-alpha


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