CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow - 04/11/20

Doi : 10.1016/j.jaci.2020.02.034

Lena Fischer-Riepe, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Niklas Daber, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Jonas Schulte-Schrepping, MSc ^b, Bruna Caroline Véras De Carvalho, MSc ^a, Antonella Russo, PhD ^a, Michele Pohlen, MD ^a,^c, Josephine Fischer, PhD ^d, Achmet Imam Chasan, PhD ^a, Marc Wolf, PhD ^a, Thomas Ulas, PhD ^b, Shirin Glander, PhD ^e, Christian Schulz, MD ^f,^g, Boris Skryabin, PhD ^h, Andreas Wollbrink, Dipl-Ing ⁱ, Nadine Steingraeber ⁱ, Christopher Stremmel, MD ^f, Megan Koehle, MD ^f, Florian Gärtner, MD ^f, Sabine Vettorazzi, PhD ^j, Dirk Holzinger, MD ^a, Joachim Gross, PhD ⁱ, Frank Rosenbauer, PhD ^d, Monika Stoll, PhD ^e, Silke Niemann, PhD ^k, Jan Tuckermann, PhD ^j, Joachim L. Schultze, MD ^b,^l, Johannes Roth, MD ^a,^m, Katarzyna Barczyk-Kahlert, PhD ^a,^⁎
^a Institute of Immunology, University of Muenster, Muenster, Germany
^b Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
^c Department of Medicine A, Hematology and Oncology, University Hospital of Muenster, Muenster, Germany
^d Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany
^e Institute of Human Genetics, Genetic Epidemiology, University of Muenster, Muenster, Germany
^f Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
^g DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
^h Department of Medicine, Transgenic Animal and Genetic Engineering Models, University of Muenster, Muenster, Germany
ⁱ Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany
^j Institute of Comparative Molecular Endocrinology (CME), University of Ulm, Ulm, Germany
^k Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany
^l Platform for Single Cell Genomics and Epigenomics (PRECISE) at the DZNE and the University of Bonn, Bonn, Germany
^m Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany

^∗Corresponding author: Katarzyna Barczyk-Kahlert, PhD, Institute of Immunology, University of Muenster, Roentgenstrasse 21, D-48149 Muenster, Germany.Institute of ImmunologyUniversity of MuensterRoentgenstrasse 21MuensterD-48149Germany

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 sought to examine 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 wild-type and CD163^−/− mice.

Results

We describe a subpopulation of bone marrow–resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow–derived macrophages. Development of CD163⁺ BMRMs is strictly dependent on IFN regulatory factor-8. CD163⁺ BMRMs 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. However, CD163^−/− mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well.

Conclusions

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 that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

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Graphical abstract

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Key words : Resident bone marrow macrophages, scavenger receptor CD163, IFN regulatory factor 8, sterile and systemic inflammation

Abbreviations used : ACD, BM, BMC, BMC w/o BMRM, BMDM, BMRM, CSF-1, DE, DEX, GO, GR, MACS, MAF, PE, ROS, WT

Plan

This work was supported by grants of the Interdisciplinary Center of Clinical Research at the University of Muenster (grant no. Ro2/003/15 to J.R.) and the German Research Foundation (Deutsche Forschungsgmeinschaft; DFG) Collaborative Research Center (CRC) 1009 B1, B9, and Z2 to S.N. and J.R., CRC Transregio 34, C13(N), DFG CRU 342 P3, and Mye-EUNITER to K.B-K. and J.R., the Excellence Cluster ImmunoSensation to J.L.S., the Excellence Cluster “Cells in Motion” to J.R., and the CRC 914 (A10) as well as the Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK; German Centre for Cardiovascular Research, High Risk High Volume) and the BMBF (Bundesministerium für Bildung und Forschung; German Ministry of Education and Research) to C.Sch. C.Str. was supported by a Gerok position of the CRC 914.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Vol 146 - N° 5

P. 1137-1151 - novembre 2020 Retour au numéro

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CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow - 04/11/20

Abstract

Background

Objectives

Methods

Results

Conclusions

Graphical abstract

Plan

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