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

J Allergy Clin Immunol. 2020 Nov;146(5):1137-1151. doi: 10.1016/j.jaci.2020.02.034. Epub 2020 Mar 19.


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.

Keywords: IFN regulatory factor 8; Resident bone marrow macrophages; scavenger receptor CD163; sterile and systemic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dermatitis, Allergic Contact / immunology*
  • Disease Models, Animal
  • Disease Susceptibility
  • Humans
  • Immunomodulation
  • Inflammation / immunology*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / physiology*
  • Transcriptome


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Cytokines
  • Interferon Regulatory Factors
  • Receptors, Cell Surface
  • interferon regulatory factor-8