Cholangiocyte biology

Cholangiocytes, the epithelial cells that line the biliary tree, are the target cells for a group of liver diseases known as the cholangiopathies. Even though cholangiocytes constitute only 4-5 % of the liver cell population, their functions are ubiquitous and range from modification of primary bile via secretion and absorption of water, electrolytes, and other molecules to the reaction of the biliary tract to exogenous insults. These cells are equipped with the machinery to recognize and respond to potentially harmful, endogenous, as well as exogenous microbial-derived molecules. Responses to cholangiocyte injury include: (1) proliferation and ductular expansion; (2) release of pro-inflammatory molecules that recruit and activate resident and nonresident immune cells to respond to infectious and inflammatory injury and promote epithelial repair; and (3) the induction of key cellular processes, including apoptosis, autophagy, and senescence. Dysregulation of these responses likely plays an active role in the development of some if not all of the cholangiopathies. In this chapter, we review selected aspects of the normal biology of cholangiocytes and address the plasticity these cells exhibit when alterations in their microenvironment occur.