Transcriptional and functional profiling defines human small intestinal macrophage subsets

被引:148
作者
Bujko, Anna [1 ,2 ]
Atlasy, Nader [3 ,4 ]
Landsverk, Ole J. B. [1 ,2 ]
Richter, Lisa [1 ,2 ]
Yaqub, Sheraz [5 ]
Horneland, Rune [6 ]
Oyen, Ole [6 ]
Aandahl, Einar Martin [6 ,8 ]
Aabakken, Lars [7 ]
Stunnenberg, Hendrik G. [3 ,4 ]
Baekkevold, Espen S. [1 ,2 ]
Jahnsen, Frode L. [1 ,2 ]
机构
[1] Univ Oslo, Dept Pathol, Ctr Immune Regulat, Oslo, Norway
[2] Oslo Univ Hosp, Rikshosp, Oslo, Norway
[3] Radboud Univ Nijmegen, Fac Sci, Radboud Inst Mol Life Sci, Dept Mol Biol, Nijmegen, Netherlands
[4] Radboud Univ Nijmegen, Fac Med, Radboud Inst Mol Life Sci, Dept Mol Biol, Nijmegen, Netherlands
[5] Oslo Univ Hosp, Rikshosp, Dept Gastrointestinal Surg, Oslo, Norway
[6] Oslo Univ Hosp, Rikshosp, Dept Transplantat Med, Oslo, Norway
[7] Oslo Univ Hosp, Rikshosp, Dept Gastroenterol, Oslo, Norway
[8] Univ Oslo, Ctr Mol Med Norway, Oslo, Norway
基金
欧洲研究理事会;
关键词
DENDRITIC CELLS; INTERLEUKIN-10-DEFICIENT MICE; MYELOID CELLS; RECEPTOR; EXPRESSION; MONOCYTES; CYTOKINE; TRANSPLANTATION; MUTATIONS; REJECTION;
D O I
10.1084/jem.20170057
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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.
引用
收藏
页码:441 / 458
页数:18
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