Transcriptional and functional profiling defines human small intestinal macrophage subsets

Anna Bujko, Nader Atlasy, Ole J.B. Landsverk, Lisa Richter, Sheraz Yaqub, Rune Horneland, Ole Øyen, Einar Martin Aandahl, Lars Aabakken, Hendrik G. Stunnenberg, Espen S. Bækkevold, Frode L. Jahnsen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

128 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)441-458
Aantal pagina's18
TijdschriftJournal of Experimental Medicine
Volume215
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - 1 feb. 2018
Extern gepubliceerdJa

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