In the steady state, hepatic antigen (Ag)-presenting cells (APC) generally dampen systemic inflammatory responses to gut-derived Ags. Our studies focus on the role of specific liver APC populations, both non-parenchymal cells (dendritic cells [DC], Kupffer cells, and hepatic stellate cells [HSC]) and parenchymal cells, in the molecular regulation of tissue damage (ischemia and reperfusion [I/R] injury) and immunity following liver transplantation. We focus on factors that either promote or overwhelm the natural tendency of the liver to suppress inflammatory/immune responses. We are also examining molecular mechanisms that regulate liver DC maturation and function and that determine their role in the control of allogeneic T-cell function and the fate of the transplanted liver. Our studies are also aimed at elucidating mechanisms by which HSC regulate DC and T-cell function. These investigations may provide new targets for therapeutic intervention in liver inflammation.