| First Author | Lisbonne M | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 6 | Pages | 1720-32 |
| PubMed ID | 21469102 | Mgi Jnum | J:176635 |
| Mgi Id | MGI:5292323 | Doi | 10.1002/eji.201041006 |
| Citation | Lisbonne M, et al. (2011) Invariant natural killer T-cell-deficient mice display increased CCl -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration. Eur J Immunol 41(6):1720-32 |
| abstractText | 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 (Jalpha18(-/-) ) 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 Jalpha18(-/-) 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 Jalpha18(-/-) 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. |
