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  • Title: CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow.
    Author: Fischer-Riepe L, Daber N, Schulte-Schrepping J, Véras De Carvalho BC, Russo A, Pohlen M, Fischer J, Chasan AI, Wolf M, Ulas T, Glander S, Schulz C, Skryabin B, Wollbrink Dipl-Ing A, Steingraeber N, Stremmel C, Koehle M, Gärtner F, Vettorazzi S, Holzinger D, Gross J, Rosenbauer F, Stoll M, Niemann S, Tuckermann J, Schultze JL, Roth J, Barczyk-Kahlert K.
    Journal: J Allergy Clin Immunol; 2020 Nov; 146(5):1137-1151. PubMed ID: 32199911.
    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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