Cholangiopathies comprise a spectrum of chronic intra- and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis and often cirrhosis and its sequela. Treatment for these diseases is limited and collectively they are one of the therapeutic “black boxes” in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators, but also common cellular and molecular events driving disease progression (e.g., cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, which are central to the pathogenesis of these disorders. Current information suggests that cholangiocytes function as a signaling “hub” in biliary tract-associated injury. Herein, we review the pivotal role of cholangiocytes in cholestatic fibrogenesis, focusing on crosstalk between cholangiocytes and portal fibroblasts and hepatic stellate cells. The proclivity of these cells to undergo a senescence-associated secretory phenotype which is pro-inflammatory and –fibrogenic, and the intrinsic intracellular activation pathways resulting in secretion of cytokines and chemokines is reviewed. The crosstalk between cholangiocytes and cells of the innate (neutrophils and macrophages), and adaptive (T-cells and B-cells) immune systems is also examined in detail. The information will help consolidate information on this topic, guide further research and potential therapeutic strategies for these diseases.

中文翻译：

---

胆管细胞病理生物学在胆汁淤积性肝病中的核心作用


胆管病包括一系列慢性肝内和肝外胆道疾病，最终导致进行性胆汁淤积性肝损伤、纤维化，通常还有肝硬化及其后遗症。这些疾病的治疗是有限的，它们共同成为临床肝病学中的治疗“黑匣子”之一。胆管病的发病机制可能包括疾病特异性介质，但也包括驱动疾病进展的常见细胞和分子事件（例如胆汁淤积纤维生成、炎症和胆管损伤）。常见途径涉及胆管细胞，即肝内和肝外胆管内衬的上皮细胞，它们是这些疾病发病机制的核心。目前的信息表明，胆管细胞在胆道相关损伤中起信号“枢纽”的作用。在此，我们回顾了胆管细胞在胆汁淤积纤维化中的关键作用，重点关注胆管细胞与门静脉成纤维细胞和肝星状细胞之间的串扰。回顾了这些细胞经历促炎和纤维化的衰老相关分泌表型的倾向，以及导致细胞因子和趋化因子分泌的内在细胞内激活途径。还详细研究了胆管细胞与先天性细胞（中性粒细胞和巨噬细胞）和适应性（T 细胞和 B 细胞）免疫系统细胞之间的串扰。这些信息将有助于整合有关该主题的信息，指导这些疾病的进一步研究和潜在治疗策略。