Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating...

Area of Science:

• Immunology
• Cell Biology
• Hematology

Background:

• The prevailing view posits that tissue macrophages originate from circulating monocytes.
• However, recent evidence suggests local self-maintenance mechanisms for tissue-resident macrophages.

Purpose of the Study:

• To investigate the contribution of circulating monocytes to tissue macrophage populations in the steady state.
• To elucidate the mechanisms of lung macrophage repopulation following depletion.
• To assess the functional capacity of host macrophages during compromised donor macrophage development.

Main Methods:

• Parabiosis and fate-mapping experiments to track monocyte contribution.
• Macrophage depletion and subsequent repopulation analysis in vivo.
• Bone marrow transplantation models, including those with genetic deficiencies.

Main Results:

• Monocytes do not significantly contribute to tissue macrophages in the steady state.
• Lung macrophage repopulation primarily occurs through local proliferation, dependent on macrophage colony-stimulating factor (M-Csf) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
• Host macrophages retain expansion capacity and provide functional protection against alveolar proteinosis even when donor macrophage development is impaired.

Conclusions:

• Tissue-resident macrophages and circulating monocytes represent distinct mononuclear phagocyte lineages.
• These lineages are maintained independently in the steady state, challenging traditional hematopoietic models.