Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity.

Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity.
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DOI:
10.1038/mi.2017.55
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发表时间:
2018-03
期刊:
影响因子:
8
通讯作者:
Colgan SP
Colgan SP
中科院分区:
医学1区
文献类型:
--
作者:
Kuhn KA;Schulz HM;Regner EH;Severs EL;Hendrickson JD;Mehta G;Whitney AK;Ir D;Ohri N;Robertson CE;Frank DN;Campbell EL;Colgan SP

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微生物群和远端肠道之间的相互作用对于维持健康的肠道屏障很重要;肠道微生物群落的生态失调已成为引起粘膜水平疾病的可能因素。上皮内淋巴细胞(IELs)位于上皮屏障内,在小肠中起维持上皮稳态的作用。我们假设结肠IELs通过表达与共生菌相互作用的细胞因子来促进上皮屏障功能。16S rRNA分析显示,拟杆菌目的候选细菌足以促进IEL在结肠中的存在,进而以myd88依赖性的方式产生IL-6。IL-6衍生的IL-6在维持上皮屏障方面具有重要的功能,因为IL-6 - / -小鼠的细胞旁通透性增加,cladin -1表达减少,黏液凝胶层更薄,所有这些都可以通过IL-6+/+ iel的转移而逆转,从而导致小鼠对啮齿柠檬酸杆菌感染的保护。因此,我们得出结论,微生物群通过调节il来源的IL-6,为上皮屏障功能提供了稳态作用。
Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine, function to maintain epithelial homeostasis. We hypothesized that colonic IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria. 16S rRNA profiling revealed that candidate bacteria in the order Bacteroidales are sufficient to promote IEL presence in the colon, which in turn, produce IL-6 in a MyD88-dependent fashion. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6−/− mice were noted to have increased paracellular permeability, decreased claudin-1 expression, and a thinner mucus-gel layer, all of which were reversed by transfer of IL-6+/+ IELs, leading to protection of mice in response to Citrobacter rodentium infection. Therefore, we conclude that microbiota provide a homeostatic role for epithelial barrier function through regulation of IEL-derived IL-6.
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