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Mucosal Immunol. 2018 Sep;11(5):1512-1523. doi: 10.1038/s41385-018-0060-1. Epub 2018 Jul 23.

Transcriptional profiling reveals monocyte-related macrophages phenotypically resembling DC in human intestine.

Author information

1
Department of Pathology, Oslo University Hospital, Oslo, Norway. l.richter@med.uni-muenchen.de.
2
Centre for Immune Regulation, University of Oslo, Oslo, Norway. l.richter@med.uni-muenchen.de.
3
Core Facility Flow Cytometry, Biomedical Center Munich, Ludwig-Maximilians-University Munich, 82152, Planegg-Martinsried, Germany. l.richter@med.uni-muenchen.de.
4
Department of Pathology, Oslo University Hospital, Oslo, Norway.
5
Centre for Immune Regulation, University of Oslo, Oslo, Norway.
6
Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute of Molecular Life Sciences, Radboud University, Nijmegen, Netherlands.
7
Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.
8
Department of Transplantation Medicine, Section for Transplant Surgery, Oslo University Hospital, Oslo, Norway.
9
Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway.
10
Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
11
K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
12
Department of Pathology, Oslo University Hospital, Oslo, Norway. frode.lars.jahnsen@rr-research.no.
13
Centre for Immune Regulation, University of Oslo, Oslo, Norway. frode.lars.jahnsen@rr-research.no.

Abstract

The tissue dendritic cell (DC) compartment is heterogeneous, and the ontogeny and functional specialization of human tissue conventional DC (cDC) subsets and their relationship with monocytes is unresolved. Here we identify monocyte-related CSF1R+Flt3- antigen presenting cells (APCs) that constitute about half of the cells classically defined as SIRPα+ DCs in the steady-state human small intestine. CSF1R+Flt3- APCs express calprotectin and very low levels of CD14, are transcriptionally related to monocyte-derived cells, and accumulate during inflammation. CSF1R+Flt3- APCs show typical macrophage characteristics functionally distinct from their Flt3+ cDC counterparts: under steady-state conditions they excel at antigen uptake, have a lower migratory potential, and are inefficient activators of naïve T cells. These results have important implications for the understanding of the ontogenetic and functional heterogeneity within human tissue DCs and their relation to the monocyte lineage.

PMID:
30038215
DOI:
10.1038/s41385-018-0060-1
[Indexed for MEDLINE]

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