Macrophages are highly heterogeneous tissue-resident immune cells that perform a variety of tissue-supportive functions. The current paradigm dictates that intestinal macrophages are continuously replaced by incoming monocytes that acquire a pro-inflammatory or tissue-protective signature. Here, we identify a self-maintaining population of macrophages that arise from both embryonic precursors and adult bone marrow-derived monocytes and persists throughout adulthood. Gene expression and imaging studies of self-maintaining macrophages revealed distinct transcriptional profiles that reflect their unique localization (i.e., closely positioned to blood vessels, submucosal and myenteric plexus, Paneth cells, and Peyer's patches). Depletion of self-maintaining macrophages resulted in morphological abnormalities in the submucosal vasculature and loss of enteric neurons, leading to vascular leakage, impaired secretion, and reduced intestinal motility. These results provide critical insights in intestinal macrophage heterogeneity and demonstrate the strategic role of self-maintaining macrophages in gut homeostasis and intestinal physiology.

中文翻译：

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自我维持的肠道巨噬细胞对于肠内稳态是必不可少的。

巨噬细胞是高度异质的组织驻留免疫细胞，其执行多种组织支持功能。当前的范例表明，肠道巨噬细胞被获得促炎或组织保护性信号的单核细胞连续替代。在这里，我们确定了由胚胎前体和成年骨髓衍生的单核细胞产生并自始至终持续存在的巨噬细胞的自我维持种群。对自我维持型巨噬细胞的基因表达和成像研究显示出独特的转录谱，反映了它们的独特定位（即紧靠血管，粘膜下层和肌层神经丛，Paneth细胞和Peyer斑块）。自养巨噬细胞的耗竭导致粘膜下血管的形态异常和肠神经元的丧失，导致血管渗漏，分泌受损和肠蠕动降低。这些结果提供了肠道巨噬细胞异质性的关键见解，并证明了自我维持巨噬细胞在肠道稳态和肠道生理中的战略作用。