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

Fischer-Riepe, Lena; Daber, Niklas; Schulte-Schrepping, Jonas; De Carvalho, Brune Caroline Veras; Russo, Antonella; Pohlen, Michele; Fischer, Josephine; Chasan, Achmet Imam; Wolf, Marc; Ulas, Thomas; Glander, Shirin; Schulz, Christian; Skryabin, Boris; Andreas Wollbrink, Dipl-Ing; Steingraeber, Nadine; Stremmel, Christopher; Koehle, Megan; Gaertner, Florian; Vettorazzi, Sabine; Holzinger, Dirk; Gross, Joachim; Rosenbauer, Frank; Stoll, Monika; Niemann, Silke; Tuckermann, Jan; Schultze, Joachim L.; Roth, Johannes und Barczyk-Kahlert, Katarzyna (2020): CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow. In: Journal of Allergy and Clinical Immunology, Bd. 146, Nr. 5: S. 1137-1151

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0091-6749
• Sprache: Englisch