The biliary tree in health and immune-mediated disease

The liver is the largest solid intra-abdominal organ and is involved in several homeostatic processes. One key role of the hepatocytes is the production of bile, a fluid that among other functions supports food digestion and via the biliary tree joins the gut contents at the level of the duodenum. Of all solutes in bile, bile salts arguably have the most profound impact on digestion and intestinal signalling. Forming the border beween the liver stroma and the lumen of the biliary tree the biliary epithelium is constantly exposed to the potentially toxic solutes of bile. Apparently, cells in the biliary epithelium have evolved effective protective mechanisms, but the exact nature of these mechanisms are incompletely understood. The experimental data presented in part 1 of this thesis adds to our understanding of how the biliary epithelium protects itself against toxic bile salts. Part 2 of this thesis focuses on immune-mediated disease of the biliary tree in general and immunoglobulin G4-related pancreaticobiliary disease in particular. The research in this part provides new insights into the clinical phenotype, etiology and treatment strategies for this rare disorder