Transcriptional and functional profiling defines human small intestinal macrophage subsets
Open Access
- 22 December 2017
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 215 (2), 441-458
- https://doi.org/10.1084/jem.20170057
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.Funding Information
- Research Council of Norway (179573)
- Southern and Eastern Norway Regional Health Authority
- Central European University
- European Research Council (339431)
- COST
- Horizon 2020 - EU Framework Program Research and Innovation Programme
This publication has 66 references indexed in Scilit:
- Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ MonocytesThe Journal of Immunology, 2017
- Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult miceNature Immunology, 2014
- Intestinal macrophages and dendritic cells: what's the difference?Trends in Immunology, 2014
- Tissue-resident macrophagesNature Immunology, 2013
- Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursorsMucosal Immunology, 2013
- Rapid Accumulation of CD14+CD11c+ Dendritic Cells in Gut Mucosa of Celiac Disease after in vivo Gluten ChallengePLOS ONE, 2012
- Density of CD163+CD11c+ Dendritic Cells Increases and CD103+ Dendritic Cells Decreases in the Coeliac LesionScandinavian Journal of Immunology, 2011
- The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cellsThe Journal of Experimental Medicine, 2010
- Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell ActivationScience, 2007
- Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.JCI Insight, 1996