A Map of Toll-like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns.
A Map of Toll-like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns.
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DOI：
10.1016/j.immuni.2018.07.016
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发表时间：
2018-09-18
期刊：
影响因子：
32.4
通讯作者：
Barton GM
中科院分区：
文献类型：
--
作者：
Price AE;Shamardani K;Lugo KA;Deguine J;Roberts AW;Lee BL;Barton GM
肠上皮细胞(IECS)上的Toll样受体(TLRs)的信号转导对肠道内环境的稳定至关重要。为了在体内可视化单个TLRs的上皮表达，我们产生了五个品系的报告小鼠。这些小鼠显示，TLR的表达沿着肠道的长度变化很大。事实上，小肠(SI)IECs表达低水平的多种TLR，而结肠IECs则高度表达。TLR5仅表达于SI上皮内的Paneth细胞。肠道类器官实验表明，Paneth细胞或结肠IECs中的TLR信号诱导了一组核心的宿主防御基因，但这组基因不包括抗菌肽，而抗菌肽是由炎性细胞因子间接诱导的。这张TLR在IECS中表达和功能的综合蓝图揭示了IECS对微生物刺激反应的意想不到的多样性，与相关的报告菌株一起，为进一步研究先天性免疫提供了资源。Price等人制作了五个品系的报告小鼠，以可视化单个TLRs在肠上皮细胞(IECs)上的表达。他们的发现揭示了TLR表达的时间和空间模式以及IECS对微生物刺激的反应性的意想不到的多样性。先天免疫力。
Signaling by Toll-like receptors (TLRs) on intestinal epithelial cells (IECs) is critical for intestinal homeostasis. To visualize epithelial expression of individual TLRs in vivo, we generated five strains of reporter mice. These mice revealed that TLR expression varied dramatically along the length of the intestine. Indeed, small intestine (SI) IECs expressed low levels of multiple TLRs that were highly expressed by colonic IECs. TLR5 expression was restricted to Paneth cells in the SI epithelium. Intestinal organoid experiments revealed that TLR signaling in Paneth cells or colonic IECs induced a core set of host defense genes, but this set did not include antimicrobial peptides, which instead were induced indirectly by inflammatory cytokines. This comprehensive blueprint of TLR expression and function in IECs reveals unexpected diversity in the responsiveness of IECs to microbial stimuli, and together with the associated reporter strains, provides a resource for further study of innate immunity. Price et al generate five strains of reporter mice to visualize the expression of individual TLRs on intestinal epithelial cells (IECs). Their findings reveal unexpected diversity in the temporal and spatial patterns of TLR expression and in the responsiveness of IECs to microbial stimuli. of innate immunity.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
64.8
作者：
通讯作者：
--
Toll样受体4位于高尔基体中，并与肠上皮细胞中的内部脂多糖共定位。
DOI：
10.1084/jem.20011788
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hornef MW;Frisan T;Vandewalle A;Normark S;Richter-Dahlfors A
通讯作者：
Richter-Dahlfors A
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
29.4
作者：
Chassaing B;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT