Brandy R Lu1, Cara L Mack. 1. Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
Abstract
PURPOSE OF REVIEW: Primary biliary cirrhosis, primary sclerosing cholangitis and biliary atresia are thought to be immune-mediated cholangiopathies, however, gaps in knowledge remain with regard to the immunopathogenesis of these diseases. RECENT FINDINGS: In this review, we highlight recent investigations pertaining to the role of both innate and adaptive immunity in bile duct damage. In innate immunity, evidence is presented for the contribution of cholangiocyte toll-like receptor stimulation promoting the ongoing inflammatory response. Innate-like lymphocytes may also be critical in the early phases of small bile duct injury found in primary biliary cirrhosis. With regard to adaptive immunity, the role of specific gene deficiencies in the susceptibility to immune-mediated cholangiopathies is reviewed. Furthermore, recent work analyzing the effector mechanisms of adaptive immunity leading to bile duct epithelial apoptosis are outlined. SUMMARY: Understanding the intricacies of the inflammatory mechanisms culminating in bile duct epithelial injury are crucial to the future development of therapies aimed at halting the ongoing biliary tract destruction found in immune-mediated cholangiopathies. A paucity of research studies on primary sclerosing cholangitis was noted in this review and future research efforts should focus on primary sclerosing cholangitis, in addition to primary biliary cirrhosis and biliary atresia.
PURPOSE OF REVIEW: Primary biliary cirrhosis, primary sclerosing cholangitis and biliary atresia are thought to be immune-mediated cholangiopathies, however, gaps in knowledge remain with regard to the immunopathogenesis of these diseases. RECENT FINDINGS: In this review, we highlight recent investigations pertaining to the role of both innate and adaptive immunity in bile duct damage. In innate immunity, evidence is presented for the contribution of cholangiocyte toll-like receptor stimulation promoting the ongoing inflammatory response. Innate-like lymphocytes may also be critical in the early phases of small bile duct injury found in primary biliary cirrhosis. With regard to adaptive immunity, the role of specific gene deficiencies in the susceptibility to immune-mediated cholangiopathies is reviewed. Furthermore, recent work analyzing the effector mechanisms of adaptive immunity leading to bile duct epithelial apoptosis are outlined. SUMMARY: Understanding the intricacies of the inflammatory mechanisms culminating in bile duct epithelial injury are crucial to the future development of therapies aimed at halting the ongoing biliary tract destruction found in immune-mediated cholangiopathies. A paucity of research studies on primary sclerosing cholangitis was noted in this review and future research efforts should focus on primary sclerosing cholangitis, in addition to primary biliary cirrhosis and biliary atresia.