Gate-keeper function of the intestinal epithelium
Gate-keeper function of the intestinal epithelium
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DOI：
10.3920/bm2012.0024
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发表时间：
2013-03-01
影响因子：
5.4
通讯作者：
Brandtzaeg, P.
中科院分区：
文献类型：
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作者：
Brandtzaeg, P.
目前主要关注肠道屏障功能在平衡粘膜免疫应答中的作用。上皮细胞对外源性抗原的通透性增加是影响体表及体表以外的几种疾病发病机制中的重要原发或继发事件。上皮细胞的守门功能取决于个体的年龄（例如，G.早产儿与足月儿）、饮食、遗传学、粘液成分、肥大细胞、神经和神经肽之间的相互作用、并发感染、肠道微生物群和由母乳提供或在个体肠道中产生的分泌型伊加（SIgA）抗体的上皮保护作用。上皮屏障的完整性还取决于稳态调节机制，包括调节性T细胞的粘膜诱导，其中肠道微生物-宿主相互作用显然起决定性作用。因此，已经确定了可能对肠道中上皮细胞-细胞连接的动力学具有影响的外在和内在因素，从而增加或减少细胞旁通透性。实验表明，SIgA通常与先天性防御因子合作以保护上皮并增强其屏障功能。在缺乏SIgA的情况下，肠道细菌以调节脂肪和碳水化合物代谢的基因的表达为代价过度刺激先天上皮免疫，导致与脂质吸收不良的发展相关的上皮基因签名。这表明肠上皮屏障是防御和营养之间的交叉路口，SIgA对保持这两种功能之间的平衡至关重要。
There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders affecting body surfaces and beyond. The epithelial gate-keeper function is determined by the individual's age (e. g. preterm vs. term infant), diet, genetics, mucus composition, interactions between mast cells, nerves and neuropeptides, concurrent infection, the commensal microbiota and the epithelium-shielding effect of secretory IgA (SIgA) antibodies provided by breast milk or produced in the individual's gut. The integrity of the epithelial barrier furthermore depends on homeostatic regulatory mechanisms, including mucosal induction of regulatory T cells, where commensal microbiota-host interactions apparently play decisive roles. Thus, both extrinsic and intrinsic factors have been identified that may have an impact on the dynamics of the epithelial cell-cell junctions in the gut and thereby increase or reduce paracellular permeability. Experiments have shown that SIgA normally cooperates with innate defence factors to protect the epithelium and reinforce its barrier function. In the absence of SIgA commensal gut bacteria overstimulate innate epithelial immunity at the expense of expression of genes that regulate fat and carbohydrate metabolism, resulting in an epithelial gene signature that correlates with the development of lipid malabsorption. This shows that the intestinal epithelial barrier is a cross-road between defence and nutrition, and that SIgA is essential to keep the balance between these two functions.