Tolerance Induction in Liver

Liver is an exclusive anatomical and immunological organ that displays a considerable tolerance effect. Liver allograft acceptance is shown to occur spontaneously within different species. Although in human transplant patients tolerance is rarely seen, the severity level and cellular mechanisms of transplant rejection vary. Non-paranchymal liver cells, including Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells, and resident dendritic cells may participate in liver tolerogenicity. The mentioned cells secret anti-inflammatory cytokines such as TGF-β and IL-10 and express negative co-stimulatory molecules like PD-L1 to mediate immunosuppression. Other mechanisms such as microchimerism, soluble major histocompatibility complex and regulatory T cells may take part in tolerance induction. Understanding the mechanisms involved in liver transplant rejection/tolerance helps us to improve therapeutic options to induce hepatic tolerance.