Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Inflamm Bowel Dis. 2011 Jan;17(1):362-81. doi: 10.1002/ibd.21403. Epub 2010 Aug 19.
The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal "leakiness." Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD.
目前，炎症性肠病（IBD）的模式，包括克罗恩病（CD）和溃疡性结肠炎（UC），涉及肠道腔环境因素与遗传易感性个体中不合适的宿主免疫反应之间的相互作用。肠道黏膜屏障的进化是为了在吸收必需营养物质的同时，防止有害物质的进入和反应，从而保持微妙的平衡。在 IBD 中，肠道屏障的重要元素的破坏导致通透性缺陷。这些屏障缺陷加剧了潜在的免疫系统，随后导致组织损伤。在活动期 IBD 中，上皮表型在 CD 和 UC 中非常相似。其特征是氯离子和水分分泌增加，导致腹泻，通过细胞内和细胞旁途径增加通透性，并增加上皮细胞凋亡。似乎驱动这些变化的主要细胞因子是 CD 中的肿瘤坏死因子-α，而白细胞介素（IL）-13 在 UC 中可能更为重要。黏膜屏障的治疗性恢复将提供保护，防止由于肠道“渗漏”而导致抗原过载。在这里，我们概述了肠道黏膜屏障的关键参与者，并回顾了目前在人类和人类系统中关于 IBD 黏膜屏障功能障碍的机制的文献。
