Transcriptional and functional profiling defines human small intestinal macrophage subsets.

Transcriptional and functional profiling defines human small intestinal macrophage subsets.
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DOI:
10.1084/jem.20170057
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发表时间:
2018-02-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Jahnsen FL
Jahnsen FL
中科院分区:
其他
文献类型:
--
作者:
Bujko A;Atlasy N;Landsverk OJB;Richter L;Yaqub S;Horneland R;Øyen O;Aandahl EM;Aabakken L;Stunnenberg HG;Bækkevold ES;Jahnsen FL

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Bujko et al. describe four distinct subsets of macrophages in human small intestine that are completely replaced in transplanted duodenum. These subsets show graduated changes in their phenotypes, function, and transcriptome profiles, suggesting that they represent stages of monocyte-derived macrophage maturation in tissue. 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.
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