The immunobiology of cholangiocytes

Abstract

Cholangiocytes, the epithelial cells lining bile ducts, provide the first line of defense against lumenal microbes in the biliary system. Recent advances in biliary immunity indicate that cholangiocytes express a variety of pathogen-recognition receptors and can activate a set of intracellular signaling cascades to initiate a profound antimicrobial defense, including release of proinflammatory cytokines and chemokines, production of antimicrobial peptides and maintenance of biliary epithelial integrity. Cholangiocytes also interact with other cell types in the liver (for example, lymphocytes and Kupffer cells) through expression and release of adhesion molecules and immune mediators. Subsequently, through an intricate feedback mechanism involving both epithelial and other liver cells, a set of intracellular signaling pathways are activated to regulate the functional state of cholangiocyte responses during microbial infection. Thus, cholangiocytes are actively involved in mucosal immunity of the biliary system and represent a fine-tuned, integral component of liver immunity.

Cholangiocyte N-Ras Protein Mediates Lipopolysaccharide-induced Interleukin 6 Secretion and Proliferation

“…Upon pathogen recognition, many immune response and inflammatory genes are up-regulated, including adhesive proteins, cytokines, and chemokines (4,18,19). The TLRs, one class of pathogen recognition receptors, recognize distinct pathogen-associated molecular patterns from bacteria, viruses, protozoa, and fungi.…”

“…Although bile is thought to be sterile under normal physiological conditions, biliary epithelial cells lining bile ducts (cholangiocytes) are periodically exposed to potentially pathogenic organisms or products derived from these microbes (1)(2)(3)(4). Indeed, cholangiocytes are exposed to bacteria (5-9), viruses (10 -12), and parasites (13)(14)(15)(16).…”

“…Indeed, cholangiocytes are exposed to bacteria (5-9), viruses (10 -12), and parasites (13)(14)(15)(16). Cholangiocyte pathogen recognition promotes innate and adaptive immune responses (4,(17)(18)(19) through the expression of adhesion molecules (20 -22) and the secretion of cytokines/chemokines (23,24) and antimicrobial peptides (18,23). Thus, cholangiocytes once thought of as an exclusively secretory/absorptive epithelium with a primary role in bile modification, are now recognized as important in the hepatic proinflammatory response to microorganisms or microbially derived products.…”

NFκB p50-CCAAT/Enhancer-binding Protein β (C/EBPβ)-mediated Transcriptional Repression of MicroRNA let-7i following Microbial Infection

“…Human bile is sterile under normal physiological conditions (1); however, the biliary tract is periodically exposed to pathogens, including Escherichia coli and the protozoan parasite Cryptosporidium parvum, or pathogenderived molecules, including Gram-negative bacteria-derived lipopolysaccharide (LPS). 2 Upon pathogen recognition, a phenotypic transition occurs through which biliary epithelial cells (cholangiocytes) promote the innate and adaptive immune responses (1)(2)(3)(4). Indeed, cholangiocytes express a variety of pathogen recognition receptors and actively participate in the innate immune response through the secretion of cytokines/ chemokines (5,6), expression of adhesion molecules (7)(8)(9), and antimicrobial peptides (1,10).…”

Healing Process of the Guinea Pig Common Bile Duct after End-to-End Anastomosis: Pathological Evaluation after 6 Months

“…Biliary epithelium cells play a number of roles in the biliary system, such as contributing 30–40% of total bile secretion, participating in bile acid reabsorption and drug metabolism, and mediating immune responses [45,46,47]. Cytokines, chemokines and proinflammatory mediators released in the portal spaces or produced by the bile duct epithelial cell itself probably activate fibrogenesis, stimulate apoptotic and proliferative responses and alter the transport functions of the epithelium [48].…”