Tolerance and autoimmunity in the liver

Excerpt

Autoimmune diseases arise from the failure of immune tolerance towards self-antigens. In the liver, maintenance of immune tolerance is particularly challenging. The liver filters all blood from the intestinal tract and is thus exposed to an infinite number of nutritional and microbial antigens. Additionally, the liver harbours the large mucosal surface of the biliary system which is colonized with microbiota and exposed to environmental factors. Together with neo-antigens arising from hepatic metabolism, the liver therefore is constantly challenged to maintain tolerance against harmless antigens and to rise immune responses against harmful environmental exposure. It is presumably for this reason that the liver microenvironment—under normal circumstances—is a particularly potent inducer of immune tolerance within the organ itself, but also systemically. For example, targeting liver sinusoidal endothelial cells using nanoparticles revealed that these cells can be harnessed to induce tolerance to the central nervous system autoantigen myelin basic protein, which can prevent the development of experimental autoimmune encephalomyelitis [1]. While the tolerogenic liver microenvironment prevents immune attack in the healthy liver, it presumably also provides a survival benefit for cancer cells and hepatotropic viruses by preventing their elimination by the immune system. …