fig6

Figure 6. Overview of immune and parenchymal cells during liver injury. A steady-state migration of immature DC to the RLN and the production of IL-10 by KC and resident DC are involved in the phenomenon of tolerance to self-antigens within a healthy liver. After a virus infection, viral particles are incorporated into DC either because they become infected or through cross-priming and then migrate to the RLN, where they differentiate and activate naive T cells. Effector CD4+ T cells return to the liver and through secretion of Th1 cytokines and collaboration with activated NK cells, might contribute to the virus clearance. In an alternative view, exogenous antigen (Ag) expressed in hepatocytes can be presented to naive CD8+ T cells which after clonal expansion become efficient CTLs and secrete Th1 cytokines Under conditions of liver injury, KC play a critical role through secretion of TNF-a, TGF-b and IL-6. The latter acting on hepatocytes induces the production of the acute phase proteins. TGF-b activates the induction of fibrosis through the action of stellate cells and TNF-a plays a critical role in the induction of cholestasis. A high production of IL-10 is able to modulate the development of fibrosis. IL: interleukin; DC: dendritic cell; RLN: regional lymph node; NK: natural killer; CTL: cytotoxic T lymphocytes; KC: Kupffer cell; TNF-a: tumor necrosis factor-a; TGF-b: transforming growth factor-b; HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus (Fainboim et al.^[104])