title: Invariant natural killer T cells suppress the neutrophil inflammatory response in a mouse model of cholestatic liver damage.
abstract: OBJECTIVE
  NK1.1(+) TCRalphabeta(int) CD1-restricted T (NKT) cells are a unique subset of T lymphocytes that are believed to have an immunoregulatory role in a wide range of diseases. Most mouse NKT cells express a T-cell receptor that contains an invariant Valpha14Jalpha18 chain and recognizes antigenic glycolipids presented in association with major histocompatibility complex class Ib (CD1d) molecules. These invariant NKT (iNKT) cells have been implicated in cholestatic liver injury.
  
  
  METHODS
  We examined the role of iNKT cells in liver injury associated with biliary obstruction in mice with ligations of the common bile duct.
  
  
  RESULTS
  The number of activated iNKT cells increased markedly in the livers of mice following bile duct ligation. Plasma alanine aminotransferase levels, an indicator of liver injury, were significantly higher in iNKT cell-deficient (Jalpha18(-/-)) mice compared with wild-type mice following bile duct ligation. Photo image analysis of histologic sections confirmed that more damage was present in the livers of Jalpha18(-/-) mice; liver damage correlated with increases in keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) production as well as neutrophil sequestration. Liver injury was significantly reduced in Jalpha18(-/-) mice treated with anti-KC and anti-MIP-2 or rendered neutrophil deficient before bile duct ligation. Similarly, Jalpha18(-/-) mice that were injected with iNKT cells before bile duct ligation exhibited significant decreases in neutrophil accumulation and liver damage.
  
  
  CONCLUSIONS
  These data document the role of iNKT cells in suppressing the neutrophil proinflammatory response and neutrophil-dependent cholestatic liver damage.
authors.affiliation: Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Wintermeyer
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
authors.forename: Beth L
authors.initials: BL
authors.lastname: Hoffman
authors.forename: Martin
authors.initials: M
authors.lastname: Holub
authors.forename: Laurent
authors.initials: L
authors.lastname: Brossay
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D001651:Cholestasis, Extrahepatic / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003135:Common Bile Duct; D004195:Disease Models, Animal; D005260:Female; D006505:Hepatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007108:Immune Tolerance / Q000276:immunology*; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000637:transplantation*; D009504:Neutrophils / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D018925:Chemokines