Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebastian, Spain.
Division of Gastroenterology and Hepatology, Mayo School of Medicine and Science, Mayo Clinic, Rochester, MN, USA.
Nat Rev Gastroenterol Hepatol. 2019 May;16(5):269-281. doi: 10.1038/s41575-019-0125-y.
Cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, are highly specialized cells residing in a complex anatomic niche where they participate in bile production and homeostasis. Cholangiocytes are damaged in a variety of human diseases termed cholangiopathies, often causing advanced liver failure. The regulation of cholangiocyte transport properties is increasingly understood, as is their anatomical and functional heterogeneity along the biliary tract. Furthermore, cholangiocytes are pivotal in liver regeneration, especially when hepatocyte regeneration is compromised. The role of cholangiocytes in innate and adaptive immune responses, a critical subject relevant to immune-mediated cholangiopathies, is also emerging. Finally, reactive ductular cells are present in many cholestatic and other liver diseases. In chronic disease states, this repair response contributes to liver inflammation, fibrosis and carcinogenesis and is a subject of intense investigation. This Review highlights advances in cholangiocyte research, especially their role in development and liver regeneration, their functional and biochemical heterogeneity, their activation and involvement in inflammation and fibrosis and their engagement with the immune system. We aim to focus further attention on cholangiocyte pathobiology and the search for new disease-modifying therapies targeting the cholangiopathies.
胆管细胞是衬在肝内和肝外胆管的上皮细胞，是高度特化的细胞，位于一个复杂的解剖龛位，参与胆汁生成和稳态。胆管细胞在各种被称为胆管疾病的人类疾病中受到损伤，常常导致晚期肝功能衰竭。胆管细胞转运特性的调节机制越来越被理解，胆管细胞在胆管中的解剖和功能异质性也是如此。此外，胆管细胞在肝脏再生中起着关键作用，特别是在肝细胞再生受损时。胆管细胞在先天和适应性免疫反应中的作用也正在显现，这是一个与免疫介导的胆管疾病相关的关键问题。最后，反应性小管细胞存在于许多胆汁淤积性和其他肝脏疾病中。在慢性疾病状态下，这种修复反应会导致肝脏炎症、纤维化和癌变，是一个深入研究的课题。这篇综述强调了胆管细胞研究的进展，特别是它们在发育和肝脏再生中的作用、它们的功能和生化异质性、它们的激活以及在炎症和纤维化中的参与，以及它们与免疫系统的相互作用。我们的目的是进一步关注胆管细胞的病理生物学，并寻找针对胆管疾病的新的疾病修饰治疗方法。
