Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation

Authors
Fliegauf, Maximilian, Levard, Damien, Cardamone, Francesco, Frosch, Maximilian, Kuhn, Siegmar, Sankowski, Roman, Provinciali, Martino, Dumas, Anaelle Aurelie, Dalmau Gasull, Adrià, Aktories, Philipp, Oschwald, Alexander, Schwabenland, Marius, Scholz, Rebekka, Beyer, Marc D., Neher, Jonas J., Kollefrath, Michael, Baltas, Dimos, Reichardt, Wilfried, von Elverfeldt, Dominik, Vivien, Denis, Cupovic, Jovana, Iovino, Nicola, Rubio, Marina, Amann, Lukas, Prinz, Marco


Lab

Journal
Nature Immunology

Abstract
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. Prinz and colleagues examine the distinct functions and repopulation properties of leptomeningeal and perivascular macrophages that mediate immune responses at brain boundaries.

Keywords/Topics
Innate immune cells; Neuroimmunology

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s41590-026-02457-y

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Test d'agrippement

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