A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium.
A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium.
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DOI：
10.1042/cs20150364
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Mabbott NA
中科院分区：
文献类型：
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作者：
Mabbott NA
Man及其同事的一项新研究进一步揭示了衰老对人类小肠屏障功能的影响。在这里，简要总结了他们的发现，并讨论了更广泛的影响。在肠道中，单层上皮细胞通过紧密连接在其顶端表面密封在一起，有助于防止腔内共生微生物和致病微生物及其毒素进入宿主组织。肠上皮还通过稳定表达抗炎细胞因子和对病原体反应的炎症细胞因子，帮助维持粘膜免疫系统的稳态。尽管老年人的粘膜免疫系统功能受损，但导致这种功能急剧下降的分子机制尚不清楚。我们目前对衰老对肠上皮屏障的物理和免疫特性的影响的理解也非常有限。在这一期的《临床科学》中，Man等人进一步深入研究了衰老对人类小肠屏障功能的影响以及肠道微生物可能对其产生的影响。利用人类回肠末端活检组织，他们发现老年人肠道对溶质的渗透性，而不是大分子的渗透性，显著增加。这伴随着促炎细胞因子白细胞介素(IL)-6的表达升高，IL -6似乎调节了cladin -2的表达和上皮的溶质通透性。相反，在老年受试者的肠道中，受鞭毛蛋白刺激的IL-8合成减少，但与toll样受体5 （TLR5）表达的影响无关。这些数据为我们了解衰老对老年人肠道通透性和先天粘膜免疫反应的影响提供了重要的进展。
A new study by Man and colleagues provides further insight into the effects of aging on small intestinal barrier function in humans. Here, their findings are briefly summarised and the wider implications discussed. In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans.