Division of Gastroenterology, University Hospital, Catholic University Leuven, Leuven, Belgium.
Clin Exp Allergy. 2011 Jan;41(1):20-8. doi: 10.1111/j.1365-2222.2010.03639.x. Epub 2010 Nov 11.
Intestinal permeability is a critical feature of the gastrointestinal epithelium as it must allow an efficient passage of nutrients and restrict the entry of larger molecules, such as protein antigen, in order to facilitate appropriate immune responses towards food antigens. The proper regulation of the epithelial barrier relies on multiple, intricate physiological and immunologic mechanisms, in terms of which recent progresses regarding the cellular and molecular components have been unravelled. In genetically predisposed individuals, breakdown of oral tolerance can occur, leading to the inadequate production of allergen-specific IgE and the recruitment of mast cells in the gastrointestinal mucosa. Under such conditions, the intestinal permeability towards allergen is altered via different mechanisms, with IgE-CD23-mediated transport across the mucosa playing an important amplification role. Additionally, during the effector phase of the allergic reaction, when mast cells degranulate, a series of inflammatory mediators, such as proteases and cytokines, are released and further affects intestinal permeability. This leads to an increase in the passage of allergens and hence contributes to perpetuate the inflammatory reaction. In this review, we describe the importance of properly balanced intestinal permeability in oral tolerance induction and address the processes involved in damaging the intestinal barrier in the sensitized epithelium and during allergic reactions. We conclude by speculating on the effect of increased intestinal permeability on the onset of sensitization towards dietary antigens.
肠通透性是胃肠道上皮的一个关键特征,因为它必须允许营养物质的有效通过,同时限制较大分子(如蛋白质抗原)的进入,以促进对食物抗原的适当免疫反应。上皮屏障的适当调节依赖于多种复杂的生理和免疫机制,最近在细胞和分子成分方面取得了一些进展。在遗传易感性个体中,口服耐受可能会被打破,导致过敏原特异性 IgE 的产生不足和胃肠道黏膜中肥大细胞的募集。在这种情况下,过敏原的肠通透性通过不同的机制发生改变,IgE-CD23 介导的跨黏膜转运起着重要的放大作用。此外,在过敏反应的效应阶段,当肥大细胞脱颗粒时,会释放一系列炎症介质,如蛋白酶和细胞因子,进一步影响肠通透性。这导致过敏原的通透性增加,从而有助于持续炎症反应。在这篇综述中,我们描述了适当平衡的肠通透性在口服耐受诱导中的重要性,并讨论了致敏上皮和过敏反应过程中破坏肠屏障的相关过程。最后,我们推测增加的肠通透性对食物抗原致敏的发生的影响。