Invariant natural killer T cells contribute to chronic-plus-binge ethanol-mediated XXXX by promoting hepatic neutrophil infiltration.

@entity32 @entity5881 @entity776 @entity19 @entity48906 @entity7936 @entity9701 @entity777 @entity58 @entity99
UNASSIGNED: Neutrophil infiltration is a hallmark of @entity7936 ; however, the underlying mechanisms remain unclear. We previously reported that chronic-plus-binge ethanol feeding synergistically induces hepatic recruitment of neutrophils, which contributes to @entity99 . In this paper, we investigated the roles of invariant natural killer T (iNKT) cells in chronic-plus-binge ethanol feeding-induced hepatic neutrophil infiltration and @entity99 . Wild-type and two strains of iNKT cell-deficient @entity19 ( @entity776 - and Ja18-deficient @entity19 ) were subjected to chronic-plus-binge ethanol feeding. @entity99 and @entity32 were examined. Chronic-plus-binge ethanol feeding synergistically increased the number of hepatic iNKT cells and induced their activation, compared with chronic feeding or binge alone. iNKT cell-deficient @entity19 were protected from chronic-plus-binge ethanol-induced hepatic neutrophil infiltration and @entity99 . Moreover, chronic-plus-binge ethanol feeding markedly upregulated the hepatic expression of several genes associated with @entity32 and neutrophil recruitment in wild-type @entity19 , but induction of these genes was abrogated in iNKT cell-deficient @entity19 . Importantly, several cytokines and chemokines (e.g., @entity9701 , @entity48906 , @entity58 , @entity777 and osteopontin) involved in neutrophil infiltration were upregulated in hepatic NKT cells isolated from chronic-plus-binge ethanol-fed @entity19 compared to pair-fed @entity19 . Finally, treatment with @entity776 blocking antibody, which blocks iNKT cell activation, partially prevented chronic-plus-binge ethanol-induced @entity99 and @entity32 . Chronic-plus-binge ethanol feeding activates hepatic iNKT cells, which play a critical role in the development of early alcoholic @entity99 , in part by releasing mediators that recruit neutrophils to the liver, and thus, iNKT cells represent a potential therapeutic target for the treatment of @entity5881 .Cellular _ Molecular Immunology advance online publication, 9 February 2015; doi:10.1038/cmi.2015.06.
