title: Invariant natural killer T-cell-deficient mice display increased CCl₄ -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration.
abstract: Invariant natural killer T (iNKT) cells are involved in the intrahepatic immune response and in hepatitis. In particular, iNKT lymphocytes are responsible for hepatocyte death in concanavalin A-induced hepatitis in mice. We examined the role of iNKT cells in acute hepatitis induced by a hepatotoxic agent, carbon tetrachloride (CCl(4) ). WT and iNKT cell-deficient (Jα18(-/-) ) mice were challenged with a single dose of 2.4 g/kg CCl(4) and both hepatic physiopathology and immune responses were studied. Plasma alanine and aspartate amino-transferase levels were significantly higher in Jα18(-/-) mice than in WT mice two days after CCl(4) administration. Chemokine CXCL1/keratinocyte-derived chemokine (KC) and MMP-8 were significantly higher in iNKT cell-deficient mice than in control mice. The more severe liver injury in Jα18(-/-) mice was associated with greater leukocyte infiltrate, which was enriched in neutrophils (CD11b(+) CD11c(-) Gr-1(+) cells), in agreement with CXCL1/KC and MMP-8 levels. Complementary experiments with NK-depleted animals indicate a minor role for NK cells in the liver damage found in iNKT-deficient mice. Thus, unlike for ConA-induced hepatitis, we report that iNKT cells protect the liver against acute hepatitis induced by CCl(4) and limit neutrophil infiltration.
authors.affiliation: EA 4427 SeRAIC-IRSET, Université de Rennes, IFR 140, Rennes, France.
authors.forename: Mariette
authors.initials: M
authors.lastname: Lisbonne
authors.forename: Annie
authors.initials: A
authors.lastname: L'Helgoualc'h
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Nauwelaers
authors.forename: Bruno
authors.initials: B
authors.lastname: Turlin
authors.forename: Catherine
authors.initials: C
authors.lastname: Lucas
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000208:Acute Disease; D000409:Alanine / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006520:Hepatitis, Animal / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D022781:Hepatocytes / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
chemical_list: D054360:Chemokine CXCL1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D020784:Matrix Metalloproteinase 8; D000409:Alanine