Department of Medicine, University of Erlangen-Nuremberg, Hartmannstrasse 14, 91 054 Erlangen, Germany.
Gut. 2013 Jul;62(7):1062-71. doi: 10.1136/gutjnl-2011-301364. Epub 2012 Jun 11.
Intestinal epithelial cells (IEC) are organised as a single cell layer which covers the intestine. Their primary task is to absorb nutrients present in the intestinal lumen. However, IEC also play an important role in the immune defence of our body by building a barrier that separates the bowel wall from potentially hazardous bacteria present in the gut lumen. The life cycle of IEC is determined by the time span in which cells migrate from their place of origin at the crypt base to the villus tip, from where they are shed into the lumen. Cell death in the intestinal epithelium has to be tightly regulated and irregularities might cause pathologies. Excessive cell death has been associated with chronic inflammation as seen in patients with Crohn's disease and ulcerative colitis. While until recently apoptosis was discussed as being essential for epithelial turnover and tissue homeostasis in the intestinal epithelium, recent data using gene deficient mice have challenged this concept. Moreover, an apoptosis-independent mode of programmed cell death, termed necroptosis, has been identified and described in the intestinal epithelium. The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis.
肠上皮细胞(IEC)排列成单层,覆盖在肠道上。它们的主要任务是吸收肠道腔中存在的营养物质。然而,IEC 通过构建一个屏障,将肠壁与肠道腔中潜在的有害细菌隔离开来,从而在我们身体的免疫防御中发挥重要作用。IEC 的生命周期由细胞从隐窝底部的起源地迁移到绒毛尖端的时间跨度决定,从那里它们被排入肠腔。肠道上皮细胞的细胞死亡必须受到严格的调控,否则不规则的细胞死亡可能会导致疾病。过度的细胞死亡与克罗恩病和溃疡性结肠炎等患者中所见的慢性炎症有关。尽管直到最近,细胞凋亡才被认为对肠道上皮细胞的上皮细胞更替和组织内稳态至关重要,但最近使用基因缺陷小鼠的研究数据对这一概念提出了挑战。此外,在肠道上皮细胞中已经确定并描述了一种凋亡非依赖性的程序性细胞死亡方式,称为坏死性凋亡。本文回顾了以前关于 IEC 细胞死亡调控的研究,以及坏死性凋亡在肠道内稳态中的潜在作用。