Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 303, Issue 10, Pages G1077-G1086Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00227.2012
Keywords
toll-like receptor; interleukin-6; interleukin-8; tumor necrosis factor-alpha; monocyte chemoattractant protein-1; interferon-gamma; defensins; Mx proteins; trefoil factors
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [R56 DK-070849, R01 DK-076735]
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Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra-and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis.
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