The healthy biliary tree: Cellular and immune biology

The biliary tree is an arborizing system of intra- and extrahepatic conduits connecting the liver to the intestine. The biliary tree has a complex tridimensional structure, encompassing bile ducts of different sizes, morphologies, and functions. The most studied function of biliary epithelial cells (cholangiocytes) is to regulate the hydration and alkalinity of the primary bile secreted by hepatocytes. An increasing number of evidence highlight the ability of cholangiocyte to undergo changes in phenotype, proliferation, and secretory activity in response to liver damage. Cholangiocytes are involved in biliary innate immunity; altered biliary innate immunity plays a role in a number of biliary diseases, including genetic cholangiopathies, such as cystic fibrosis-related liver disease. In addition, cholangiocytes may behave as antigen-presenting cells and secrete immunoglobulins as well as several antimicrobial peptides. Thus, cholangiocytes, by participating actively to the immune and inflammatory responses, represent a first defense line against liver injury from different causes. In fact, cholangiocytes possess a number of sensing receptors for pathogen-associated molecular patterns (PAMPs), such as Toll-like receptors (TLRs), which modulate their proinflammatory behavior. Derangements of the signals controlling these mechanisms are at the basis of the pathogenesis of different cholangiopathies, often extending beyond the classically recognized immune-mediated (primary biliary cirrhosis, primary sclerosing cholangitis), as in cystic fibrosis liver diseas