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CCR5 deficiency exacerbates T‐cell–mediated hepatitis in mice
Author(s) -
Moreno Christophe,
Gustot Thierry,
Nicaise Charles,
Quertinmont Eric,
Nagy Nathalie,
Parmentier Marc,
Le Moine Olivier,
Devière Jacques,
Louis Hubert
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20865
Subject(s) - ccl5 , chemokine , ccl4 , liver injury , chemokine receptor ccr5 , peripheral blood mononuclear cell , ccl3 , ccr5 receptor antagonist , concanavalin a , hepatitis , tumor necrosis factor alpha , immunology , chemokine receptor , t cell , biology , chemistry , inflammation , endocrinology , ccl2 , il 2 receptor , in vitro , immune system , biochemistry , carbon tetrachloride , organic chemistry
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 α, 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 immunomediated liver injury. (H EPATOLOGY 2005;42:854–862.)