Transcriptional and functional profiling defines human small intestinal macrophage subsets

  • Anna Bujko
    Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway 1
  • Nader Atlasy
    Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute of Molecular Life Sciences, Radboud University, Nijmegen, Netherlands 2
  • Ole J.B. Landsverk
    Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway 1
  • Lisa Richter
    Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway 1
  • Sheraz Yaqub
    Department of Gastrointestinal Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway 3
  • Rune Horneland
    Department for Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway 4
  • Ole Øyen
    Department for Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway 4
  • Einar Martin Aandahl
    Department for Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway 4
  • Lars Aabakken
    Department for Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway 5
  • Hendrik G. Stunnenberg
    Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute of Molecular Life Sciences, Radboud University, Nijmegen, Netherlands 2
  • Espen S. Bækkevold
    Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway 1
  • Frode L. Jahnsen
    Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway 1

説明

<jats:p>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.</jats:p>

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