Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis
Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis
复制标题
自我维持的肠道巨噬细胞对肠道内稳态至关重要
DOI：
10.1016/j.cell.2018.07.048
复制
发表时间：
2018-10-04
期刊：
影响因子：
64.5
通讯作者：
Boeckxstaens, Guy
中科院分区：
文献类型：
--
作者：
De Schepper, Sebastiaan;Verheijden, Simon;Boeckxstaens, Guy
巨噬细胞是执行多种组织支持功能的高度异质的组织驻留免疫细胞。目前的范式表明，肠道巨噬细胞不断被获得促炎或组织保护特征的传入单核细胞取代。在这里，我们确定了一个自我维持的人口巨噬细胞产生的胚胎前体细胞和成人骨髓来源的单核细胞，并持续整个成年期。自我维持巨噬细胞的基因表达和成像研究揭示了反映其独特定位的不同转录谱（即，靠近血管、粘膜下和肌间神经丛、潘氏细胞和派伊尔集合淋巴结）。自我维持的巨噬细胞的消耗导致粘膜下脉管系统的形态异常和肠神经元的损失，导致血管渗漏、分泌受损和肠动力降低。这些结果提供了关键的见解，在肠道巨噬细胞异质性，并证明了自我维持巨噬细胞在肠道内稳态和肠道生理学的战略作用。
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.