Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation - PubMed
3 hours ago
- #neurodegenerative diseases
- #neuroimmunology
- #CNS macrophages
- Nonparenchymal CNS-associated macrophages (CAMs) mediate immune responses at brain boundaries.
- Subdural CAMs (sdCAMs) and microglia originate from embryonic yolk sac precursors and maintain populations through self-renewal.
- Microglia repopulate autonomously from single surviving cells after depletion, while sdCAM repopulation dynamics differ.
- sdCAMs do not renew cell-autonomously but become accessible to CCR2+Ly6C+ monocyte engraftment in an integrin-dependent manner after niche induction.
- Monocyte-derived sdCAMs remain distinct from embryo-derived sdCAMs in transcriptomic, epigenetic, and functional aspects.
- A protocol for selective exchange of sdCAMs is presented, which modulates disease response without affecting microglia.
- These findings suggest new therapeutic avenues for neuroinflammatory and neurodegenerative diseases.