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转录组和功能谱分析定义了人类小肠巨噬细胞亚群。

Transcriptional and functional profiling defines human small intestinal macrophage subsets.

机构信息

Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway

Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute of Molecular Life Sciences, Radboud University, Nijmegen, Netherlands.

出版信息

J Exp Med. 2018 Feb 5;215(2):441-458. doi: 10.1084/jem.20170057. Epub 2017 Dec 22.

DOI:10.1084/jem.20170057
PMID:29273642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5789404/
Abstract

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.

摘要

巨噬细胞（Mfs）在维持肠道免疫稳态方面起着重要作用，但关于人类肠道 Mfs 的起源和异质性的研究还很缺乏。在这里，我们在人类小肠（SI）中鉴定出了四个不同的 Mf 亚群。评估它们在十二指肠移植中的周转率表明，所有 Mf 亚群都会随着时间的推移而被完全替代；表型上类似于外周血单核细胞（PBMos）的 Mf1 和 Mf2 在 3 周内就被大量替代，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代。Mf3 和 Mf4 在 SI 中的定位不同；Mf3 在黏膜固有层中形成密集的网络，而 Mf4 在黏膜下层中富集。转录分析表明，所有 Mf 亚群都明显不同于 PBMos 和树突状细胞。与 PBMos 相比，Mf 亚群对促炎刺激的反应性降低，但擅长吞噬颗粒状和可溶性物质。这些数据提供了对人类 SI Mf 群体的全面分析，并表明与 PBMos 存在前体-后代关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/5568a9dba3bd/JEM_20170057_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/fbdb38a4a17a/JEM_20170057_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/f15767bfa7f4/JEM_20170057_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/c73d5bd9cfa5/JEM_20170057_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/f7555d5210d6/JEM_20170057_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/da84e072de28/JEM_20170057_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/bfa4f6437ed7/JEM_20170057_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/5568a9dba3bd/JEM_20170057_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/fbdb38a4a17a/JEM_20170057_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/f15767bfa7f4/JEM_20170057_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/c73d5bd9cfa5/JEM_20170057_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/f7555d5210d6/JEM_20170057_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/da84e072de28/JEM_20170057_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/bfa4f6437ed7/JEM_20170057_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3265/5789404/5568a9dba3bd/JEM_20170057_Fig7.jpg

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本文引用的文献

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Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

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Nat Immunol. 2016-1

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