| [ Summary ] |
Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic liver disease, presumably caused by autoimmune reactions against biliary epithelial cells (BEC) in the liver. Several lines of epidemiological evidence indicate the involvement of genetic components in addition to environmental factors in the susceptibility to PBC, as seen in other autoimmune diseases. Although PBC is still an enigmatic disease, there has been remarkable progresse in understanding its etiology. Several recent findings have clearly elucidated the roles of NK cells, monocytes/macrophages, dendritic cells and anti-mitochondorial antibodies in the immunopathogenesis of PBC. In addition, BECs are probably not innocent victims as previously considered, but rather active participants in disease processes, since BECs vigorously participate in the disease process by presenting autoantigens resident in BEC to antigen presenting cells. Moreover, genome-wide association studies (GWAS) have demonstrated significant associations of several loci with a susceptibility to PBC. Surely these susceptible genes help to explain how and why BECs are selectively targeted by autoimmune reactions in PBC. |