New publication by project B01 about the cellular responsiveness of CNS macrophages after repopulation

The PILOT researcher Marco Prinz showed that Monocyte-derived brain macrophages are transcriptomically, epigenetically and functionally distinct from fetal macrophages and that brain border macrophage dynamics are distinct from the parenchyma.

The article "Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation" was recently published in Nature Immunology.

Nonparenchymal central nervous system (CNS)-associated macrophages (CAMs) mediate immune responses at brain boundaries. Perivascular and leptomeningeal CAMs are collectively termed subdural CAMs (sdCAMs). Both sdCAMs and juxtaneuronal microglia are derived from embryonic yolk sac precursors, long-living and maintain their populations through self-renewal. Following depletion, microglia autonomously repopulate from single surviving cells. In contrast, the course of sdCAM repopulation remains poorly understood. Here, by combining multilineage fate mapping, multiomic profiling and high-resolution imaging, we demonstrate divergent repopulation dynamics between sdCAMs and microglia. Unlike microglia, sdCAMs do not renew cell-autonomously, but become transiently accessible to CCR2+Ly6C+ monocyte engraftment after niche induction in an integrin-dependent manner. Moreover, replenished monocyte-derived sdCAMs remain transcriptomically, epigenetically and functionally distinct from their embryo-derived counterparts. Finally, we present a protocol enabling selective exchange of sdCAMs, modulating disease response without functionally affecting microglia. These new insights into CNS immune biology suggest new therapeutic avenues for neuroinflammatory and neurodegenerative diseases.

Read the full publication here: https://doi.org/10.1038/s41590-026-02457-y