Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.

巨噬细胞（Mfs）有助于维持肠道免疫稳态，但对人类肠道 Mfs 的起源和异质性的研究很少。在这里，我们鉴定了人类小肠 (SI) 中的四个不同的 Mf 亚群。对十二指肠移植中的更新率的评估显示，随着时间的推移，所有 Mf 亚群都被完全替换； Mf1 和 Mf2 表型与外周血单核细胞 (PBMos) 相似，在 3 周内大部分被替换，而具有成熟 Mfs 特征的两个亚群 Mf3 和 Mf4 则表现出明显较慢的替换。 Mf3 和 Mf4 在 SI 中的定位不同； Mf3 在粘膜固有层形成致密网络，而 Mf4 在粘膜下层富集。转录分析表明所有 Mf 亚群均与 PBMos 和树突状细胞显着不同。与PBMos相比，Mf亚群对​​促炎刺激的反应性降低，但擅长颗粒和可溶性物质的内吞作用。这些数据提供了对人类 SI Mf 群体的全面分析，并表明与 PBMos 之间存在前体-后代关系。