Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado; and
Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
J Appl Physiol (1985). 2017 Nov 1;123(5):1321-1327. doi: 10.1152/japplphysiol.00113.2017. Epub 2017 Jul 13.
Epithelial cells of the mucosa provide a first line of defense to prevent the inappropriate translocation of luminal antigens, and therefore contribute significantly to nonspecific innate immunity. In the gastrointestinal (GI) tract, barrier is provided by multiple components of the mucosa, including mucus production, epithelial junctional complexes, and the production of antimicrobial molecules. In recent years, it is better appreciated that tissue oxygen metabolism is key to homeostasis in the mucosa. The intestine, for example, maintains a low baseline Po level due to high rates of metabolism, countercurrent blood flow, and the presence of a steep oxygen gradient across the luminal aspect of tissue surface. As a result, hypoxia and hypoxia-inducible factor (HIF)-dependent signaling exists even in the healthy, unperturbed intestinal mucosa. In a number of examples, HIF has been demonstrated both to promote barrier function during homeostasis and to promote resolution of active inflammation. Hypoxia-elicited factors that contribute to innate responses in the mucosa include the transcriptional regulation of mucin genes, junction proteins, and autophagic flux. Here, we review current literature related to hypoxia and innate immunity in health and during mucosal inflammation.
黏膜上皮细胞构成了防止腔抗原不当移位的第一道防线，因此对非特异性先天免疫有重要贡献。在胃肠道（GI）中，黏膜的多种成分提供了屏障，包括黏液产生、上皮连接复合体和抗菌分子的产生。近年来，人们越来越认识到组织氧代谢是黏膜内稳态的关键。例如，由于代谢率高、逆流血流和组织表面腔侧存在陡峭的氧梯度，肠道保持着较低的基础 Po 水平。因此，即使在健康、未受干扰的肠道黏膜中，也存在缺氧和缺氧诱导因子（HIF）依赖性信号。在许多情况下，已经证明 HIF 既可以在稳态期间促进屏障功能，也可以促进活跃炎症的消退。缺氧引起的促进黏膜固有反应的因素包括粘蛋白基因、连接蛋白和自噬流的转录调控。在这里，我们综述了与健康和黏膜炎症期间缺氧和先天免疫相关的当前文献。
