Liver sinusoidal endothelial cells: a new type of organ-resident antigen-presenting cell.

The induction of peripheral immune tolerance in the liver is a well-known phenomenon that is operative in different situations, such as tolerance to organ transplants and tolerance to oral antigens. The mechanisms leading to peripheral immune tolerance in the liver are still incompletely understood. While different cell populations of the liver have been implicated in and probably contribute in concert to the induction of hepatic immune tolerance, one hepatic cell type in particular seems to be suited for tolerance induction: liver sinusoidal endothelial cell (LSEC). LSEC are microvascular endothelial cells with a unique phenotype reminiscent of dendritic cells and a unique function as antigen-presenting cells for CD4+ T cells. The hepatic microenvironment, i.e. portal venous constituents and soluble mediators from sinusoidal cell populations, tightly control antigen presentation by LSEC to avoid immune-mediated damage. LSEC, in contrast to other endothelial cells, have the capacity to prime naive CD4+ T cells and induce cytokine release. Importantly, naive CD4+ T cells primed by antigen-presenting LSEC differentiate into regulatory T cells, whereas T cells primed by bone marrow-derived professional antigen presenting cells differentiate into Th1 cells. Thus, LSEC represent a new type of organ-resident "non-professional" antigen-presenting cell that appears to be involved in the local control of the immune response and the induction of immune tolerance in the liver.