Martini Eva, Krug Susanne M, Siegmund Britta, Neurath Markus F, Becker Christoph
Medical Clinic 1, Friedrich-Alexander-University, Erlangen, Germany.
Institute of Clinical Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Cell Mol Gastroenterol Hepatol. 2017 Mar 23;4(1):33-46. doi: 10.1016/j.jcmgh.2017.03.007. eCollection 2017 Jul.
The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell-mediated mechanisms. Recent evidence, however, suggests that the intestinal epithelium might play a major role in the development and perpetuation of IBD. It is now clear that IBD can be triggered by disturbances in epithelial barrier integrity via dysfunctions in intestinal epithelial cell-intrinsic molecular circuits that control the homeostasis, renewal, and repair of intestinal epithelial cells. The intestinal epithelium in the healthy individual represents a semi-permeable physical barrier shielding the interior of the body from invasions of pathogens on the one hand and allowing selective passage of nutrients on the other hand. However, the intestinal epithelium must be considered much more than a simple physical barrier. Instead, the epithelium is a highly dynamic tissue that responds to a plenitude of signals including the intestinal microbiota and signals from the immune system. This epithelial response to these signals regulates barrier function, the composition of the microbiota, and mucosal immune homeostasis within the lamina propria. The epithelium can thus be regarded as a translator between the microbiota and the immune system and aberrant signal transduction between the epithelium and adjacent immune cells might promote immune dysregulation in IBD. This review summarizes the important cellular and molecular barrier components of the intestinal epithelium and emphasizes the mechanisms leading to barrier dysfunction during intestinal inflammation.
在炎症性肠病（IBD）如溃疡性结肠炎或克罗恩病中，肠道炎症期间肠上皮很容易受到破坏。长期以来，IBD病理生理学的研究一直集中在免疫细胞介导的机制上。然而，最近的证据表明，肠上皮可能在IBD的发生和持续发展中起主要作用。现在很清楚，IBD可由肠上皮屏障完整性的紊乱引发，这种紊乱是通过控制肠上皮细胞稳态、更新和修复的肠上皮细胞内在分子回路功能障碍导致的。健康个体的肠上皮代表一种半透性物理屏障，一方面保护身体内部免受病原体入侵，另一方面允许营养物质选择性通过。然而，肠上皮绝不能仅仅被视为一个简单的物理屏障。相反，上皮是一种高度动态的组织，它对包括肠道微生物群和免疫系统信号在内的大量信号作出反应。这种上皮对这些信号的反应调节屏障功能、微生物群的组成以及固有层内的黏膜免疫稳态。因此，上皮可被视为微生物群和免疫系统之间的“翻译器”，上皮与相邻免疫细胞之间异常的信号转导可能会促进IBD中的免疫失调。本综述总结了肠上皮重要的细胞和分子屏障成分，并强调了肠道炎症期间导致屏障功能障碍的机制。
