Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China.
Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1367-1373. doi: 10.1016/j.bbadis.2017.08.019. Epub 2017 Aug 24.
The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines. However, breach of tolerance in the biliary tree results in various cholangiopathies, exemplified by primary biliary cholangitis, primary sclerosing cholangitis and biliary atresia. Lessons learned from immune tolerance of the biliary tree will provide the basis for the development of effective therapeutic approaches against autoimmune biliary tract diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
肝脏是一个具有独特解剖、组织学和异质细胞群体的重要器官。这些特征对于维持肝脏微环境（特别是胆管树）中的免疫稳态尤为重要。胆管细胞是胆管树抵御外来物质的第一道防线，并且能够通过各种免疫途径参与其中。事实上，胆管细胞通过 TLRs 相关信号来保护免受病原体的侵害；通过表达 IRAK-M 和 PPARγ 来维持耐受；通过诱导白细胞凋亡来限制免疫反应；通过表达人类白细胞抗原分子和共刺激分子来提呈抗原；通过表达细胞因子和趋化因子来招募白细胞到靶位。然而，胆管树的耐受破坏会导致各种胆管疾病，例如原发性胆汁性胆管炎、原发性硬化性胆管炎和胆道闭锁。从胆管树的免疫耐受中吸取的经验教训将为开发针对自身免疫性胆道疾病的有效治疗方法提供基础。本文是由 Jesus Banales、Marco Marzioni、Nicholas LaRusso 和 Peter Jansen 编辑的题为“健康与疾病中的胆管细胞”的特刊的一部分。
