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J Allergy Clin Immunol. 2020 Mar 18. pii: S0091-6749(20)30344-4. doi: 10.1016/j.jaci.2020.02.034. [Epub ahead of print]

CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow.

Author information

1
Institute of Immunology, University of Muenster, Muenster, Germany.
2
Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
3
Institute of Immunology, University of Muenster, Muenster, Germany; Department of Medicine A, Hematology and Oncology, University Hospital of Muenster, Muenster, Germany.
4
Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany.
5
Institute of Human Genetics, Genetic Epidemiology, University of Muenster, Muenster, Germany.
6
Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
7
Department of Medicine, Transgenic Animal and Genetic Engineering Models, University of Muenster, Muenster, Germany.
8
Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany.
9
Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
10
Institute of Comparative Molecular Endocrinology (CME), University of Ulm, Ulm, Germany.
11
Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany.
12
Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; Platform for Single Cell Genomics and Epigenomics (PRECISE) at the DZNE and the University of Bonn, Bonn, Germany.
13
Institute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany.
14
Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: bar@uni-muenster.de.

Abstract

BACKGROUND:

Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear.

OBJECTIVES:

We examined the function of CD163 in steady-state as well as in sterile and infectious inflammation.

METHODS:

Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wildtype and CD163-/- mice.

RESULTS:

We describe a subpopulation of BM resident macrophages (BMRM) which is characterized by a high expression of CD163 and is functionally distinct from classical bone marrow-derived macrophages (BMDM). Development of CD163+ BMRM is strictly dependent on interferon regulatory factor-8 (IRF8). CD163+ BMRM show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163-/- mice show a stronger inflammation in allergic contact dermatitis indicating a regulatory role of CD163. On the other hand, CD163-/- mice are highly susceptible to S. aureus infections demonstrating the relevance of CD163 for anti-microbial defense as well.

CONCLUSION:

Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population which controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

KEYWORDS:

interferon regulatory factor 8; regulation of sterile and systemic inflammation; resident bone marrow macrophages; scavenger receptor CD163

PMID:
32199911
DOI:
10.1016/j.jaci.2020.02.034

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