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Immunity. 2019 Oct 15;51(4):638-654.e9. doi: 10.1016/j.immuni.2019.08.017. Epub 2019 Sep 24.

Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche.

Author information

1
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: johnny.bonnardel@irc.vib-ugent.be.
2
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
3
Unit for Molecular Immunology and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
4
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
5
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
6
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
7
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
8
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; VIB BioImaging Core, VIB, Ghent, Belgium.
9
Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Laboratory of Mucosal Immunology and Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium.
10
Liver Cell Biology Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
11
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
12
Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
13
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: martin.guilliams@irc.vib-ugent.be.

Abstract

Macrophages are strongly adapted to their tissue of residence. Yet, little is known about the cell-cell interactions that imprint the tissue-specific identities of macrophages in their respective niches. Using conditional depletion of liver Kupffer cells, we traced the developmental stages of monocytes differentiating into Kupffer cells and mapped the cellular interactions imprinting the Kupffer cell identity. Kupffer cell loss induced tumor necrosis factor (TNF)- and interleukin-1 (IL-1) receptor-dependent activation of stellate cells and endothelial cells, resulting in the transient production of chemokines and adhesion molecules orchestrating monocyte engraftment. Engrafted circulating monocytes transmigrated into the perisinusoidal space and acquired the liver-associated transcription factors inhibitor of DNA 3 (ID3) and liver X receptor-α (LXR-α). Coordinated interactions with hepatocytes induced ID3 expression, whereas endothelial cells and stellate cells induced LXR-α via a synergistic NOTCH-BMP pathway. This study shows that the Kupffer cell niche is composed of stellate cells, hepatocytes, and endothelial cells that together imprint the liver-specific macrophage identity.

KEYWORDS:

Bmp9; Id3; Kupffer cell; LXRa; Notch; Nr1h3; endothelial cell; fibroblast; liver; macrophage; monocyte; niche; stellate cell

Comment in

PMID:
31561945
PMCID:
PMC6876284
DOI:
10.1016/j.immuni.2019.08.017
[Indexed for MEDLINE]
Free PMC Article

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