Advances in cholangiocyte immunobiology
Advances in cholangiocyte immunobiology
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DOI：
10.1152/ajpgi.00227.2012
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发表时间：
2012-11-01
影响因子：
4.5
通讯作者：
Dranoff, Jonathan A.
中科院分区：
文献类型：
--
作者：
Syal, Gaurav;Fausther, Michel;Dranoff, Jonathan A.
胆管细胞或胆管上皮细胞曾被认为是包括肝内和肝外胆管的管道系统的简单衬里。越来越多的实验证据表明，胆管细胞实际上是胆道系统抵御外来物质的第一道防线。近年来的实验进展揭示了胆管细胞在先天性和适应性免疫反应中的未知作用。胆管细胞可以以调节的方式释放炎症调节剂。此外，它们表达专门的模式识别分子，识别微生物组分并激活细胞内信号级联，导致各种下游反应。由胆管细胞分泌的细胞因子与其表面表达的粘附分子一起在肝脏和胆道中的免疫应答的募集、定位和调节中发挥作用。免疫细胞和胆管细胞自身分泌的细胞因子和炎症介质进一步调节胆管细胞的存活和功能。由于胆管细胞通过表达主要组织相容性复合物抗原和分泌胆汁中的抗菌肽来充当专职APC，因此它们在响应胆汁感染中的作用是至关重要的。最后，由于胆管细胞释放的介质门静脉成纤维细胞和肝星状细胞的肌纤维母细胞分化的关键，胆管细胞可能是必不可少的胆汁性肝硬化的发病机制。
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.