engleski

NK cell-dependent liver injury triggered by liver NKT cell activation

Activation of the liver NKT cells triggered by injection of the low dose alpha-galactosylceramide ( Gal/Cer) into mice induces liver injury. This effect is suppressed in mice depleted of NK cells, therefore NK cells recruited into this response are largely responsible for NKT-cell initiated liver injury. Our in vitro results showed that liver NKT cells provide CD80/86 dependent signal to alphaGal/Cer pulsed dendritic cells to release IL12 p70. That cytokine stimulate the IFNgamma response of NKT and NK cells. Adoptive transfer of in vitro NKT cell-activated liver dendritic cells into the liver of normal B6 mice via the portal vein elicited IFN response of liver NK cells in situ. IFNgamma down regulates the IL12/IFNgamma cytokine cascade triggered by NKT cells/DC/NK cell interactions in the liver. Pretreating liver DC in vitro with IFNgamma supressed their IL12 p70 (but not IL10 ) release in response to CD40 ligation or specific interaction with liver NKT cells, and downregulated the IFN response of the specifically activated liver NKT cells. In vivo, IFNgamma attenuate the NKT cell-triggered induction of liver immunopathology. This study identifies interacting subsets of the hepatic innate immune system activated early in immune-mediated liver pathology, and cytokines involved in these interactions.

NK cell; NKT cell; liver injury; alfa-galctosyl ceramide

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