Natural killer cells take two tolls to destruct bile ducts

Abstract

Pit cells were first described by Wisse et al.1 in 1976. Later, Kaneda et al.2 referred to this cell type as “natural killer (NK) cells” due to their resemblance to large granular lymphocytes that are known to possess NK cell activity. In 1984, Kaneda et al.3 also observed that in autoimmune hepatitis, these pit cells (now known as liver-specific NK cells) were frequently seen in close contact with hepatocytes that eventually showed degenerative or immature features, providing the first evidence that NK cells may contribute to hepatocellular damage in autoimmune hepatitis. Although more than 2 decades have since passed and the accumulating evidence indicates that NK cells are involved in the pathogenesis of many types of human autoimmune diseases,4 little is known about the role of NK cells in autoimmune liver disease specifically. To date, there are several studies reporting that NK cell functions are dysregulated in autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis (PBC). These data show that in patients with PBC, there was increased cell-killing activity and decreased cytokine production in NK cells5 and that there appeared to be a genetic link between NK cell receptor ligand expression and susceptibility to primary sclerosing cholangitis.6 However, the mechanism by which NK cells are activated and contribute to the pathogenesis of autoimmune liver disease was largely unknown until Shimoda et al.7 published their recent data in this issue of Hepatology.