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

Area of Science:

• Immunology
• Macrophage Biology
• Inflammation Research

Background:

• Scavenger receptor CD163 is a known marker for alternatively activated macrophages.
• Its precise function in immune responses remains unclear.

Purpose of the Study:

• To investigate the role of CD163 in both normal physiological conditions and during sterile and infectious inflammation.
• To elucidate the function of CD163 in different inflammatory models.

Main Methods:

• Analyzing CD163 expression in mice under normal and inflammatory conditions.
• Investigating CD163's functional importance using wild-type and CD163 knockout mice models.
• Characterizing CD163+ bone marrow-resident macrophages (BMRMs) and their dependence on IFN regulatory factor-8.

Main Results:

• A distinct subpopulation of CD163+ bone marrow-resident macrophages (BMRMs) was identified, functionally different from classical bone marrow-derived macrophages.
• These CD163+ BMRMs possess a unique transcriptome and cytokine profile, indicating a specific immunomodulatory role.
• CD163 knockout mice exhibited exacerbated allergic contact dermatitis but increased susceptibility to Staphylococcus aureus infections, highlighting CD163's dual role.

Conclusions:

• CD163 plays a critical role in regulating inflammation and host defense against infections.
• A novel macrophage population expressing CD163 is essential for controlling excessive inflammation while maintaining antimicrobial activity.
• Anti-inflammatory functions do not necessarily impair antimicrobial defense, challenging previous assumptions.