Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome
Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome
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DOI：
10.1038/s41467-020-15068-4
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发表时间：
2020-03-12
影响因子：
16.6
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
--
作者：
Honda, Masaki;Surewaard, Bas G. J.;Kubes, Paul
虽然肠道单核细胞/巨噬细胞谱系的个体发育和募集已被广泛研究，但它们的精确定位和功能却被忽视了。在这里，我们通过对稳态下的小鼠小肠和大肠进行成像表明，肠道CX3CR1（+）巨噬细胞形成了一个与整个粘膜固有层脉管系统紧密粘附的叉指网络。巨噬细胞彼此形成接触，但在缺乏微生物组、单核细胞募集 (Ccr2(-/-)) 或单核细胞转化 (Nr4a1(-/-)) 的情况下，这种接触会被破坏。在生态失调中，血管周围巨噬细胞之间存在间隙，这与细菌从固有层进入血流的移位增加相关。肠道损伤期间单核细胞的募集和巨噬细胞的转化也取决于 CCR2、Nr4a1 和微生物组。这些发现证明了微生物组与固有层血管周围巨噬细胞成熟为紧密的解剖屏障之间的关系，该屏障可能起到防止细菌易位的作用。这些细胞对于紧急血管修复也至关重要。
While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked. Here we show by imaging the murine small and large intestines in steady-state that intestinal CX3CR1(+) macrophages form an interdigitated network intimately adherent to the entire mucosal lamina propria vasculature. The macrophages form contacts with each other, which are disrupted in the absence of microbiome, monocyte recruitment (Ccr2(-/-)), or monocyte conversion (Nr4a1(-/-)). In dysbiosis, gaps exist between the perivascular macrophages correlating with increased bacterial translocation from the lamina propria into the blood-stream. The recruitment of monocytes and conversion to macrophages during intestinal injury is also dependent upon CCR2, Nr4a1 and the microbiome. These findings demonstrate a relationship between microbiome and the maturation of lamina propria perivascular macrophages into a tight anatomical barrier that might function to prevent bacterial translocation. These cells are also critical for emergency vascular repair.