Coordinated chemokine expression defines macrophage subsets across tissues.

Area of Science:

• Immunology
• Cell Biology
• Tissue-resident macrophages

Background:

• Lung-resident macrophages, including interstitial macrophages (IMs), show significant diversity.
• This diversity is influenced by activation states and monocyte infiltration.
• Understanding IM functional diversity is crucial for immune response insights.

Purpose of the Study:

• To comprehensively profile resident IMs and identify distinct subsets.
• To investigate the functional roles of IM subsets in immune regulation.
• To explore the conserved nature of IM subsets across tissues and species.

Main Methods:

• Comprehensive transcriptional profiling of resident interstitial macrophages.
• Analysis of chemokine expression patterns in distinct IM subsets.
• Depletion studies using genetic models (Pf4creR26EYFP+DTR and Pf4creR26EYFP Cx3cr1DTR mice) to assess IM function.

Main Results:

• Identification of ten distinct chemokine-expressing IM subsets at steady state and during inflammation.
• Observed conserved IM subsets and coordinated chemokine signatures across tissues and species.
• Depletion of CD206hi IMs led to reduced inflammatory cell recruitment, tertiary lymphoid structure formation, and germinal center B cells.

Conclusions:

• Interstitial macrophages possess specialized functional roles defined by coordinated chemokine production.
• IMs are critical regulators of immune cell influx and tertiary lymphoid tissue organization.
• These findings provide a deeper understanding of IM diversity and function in immunity.