RT Journal Article SR Electronic T1 Transcriptional and functional profiling defines human small intestinal macrophage subsets JF The Journal of Experimental Medicine JO J Exp Med FD Rockefeller University Press SP 441 OP 458 DO 10.1084/jem.20170057 VO 215 IS 2 A1 Bujko, Anna A1 Atlasy, Nader A1 Landsverk, Ole J.B. A1 Richter, Lisa A1 Yaqub, Sheraz A1 Horneland, Rune A1 Øyen, Ole A1 Aandahl, Einar Martin A1 Aabakken, Lars A1 Stunnenberg, Hendrik G. A1 Bækkevold, Espen S. A1 Jahnsen, Frode L. YR 2018 UL http://jem.rupress.org/content/215/2/441.abstract AB 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.