Immunity · 2026
Microglia with distinct origins and non-canonical phenotypes coexist within the border-like niche of the brain's circumventricular organs.
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Van Hove Hannah, Bastos Jonathan, Kancheva Daliya, Vara-Pérez Mónica, Dorion Marie-France, Westermann Frederike, Ulutekin Can, Shakeri Hadis, Ali Leen, Lievens Ayla Line, Mayoux Maud, Sterczyk Nele, Biscu Francesca, Meysman Laura, Scheyltjens Isabelle, De Vlaminck Karen, Pombo Antunes Ana Rita, Mildenberger Wiebke, Amann Lukas, Gomez-Nicola Diego, Smolders Ilse, Tugues Sonia, Ginhoux Florent, Prinz Marco, Scott Charlotte L, Becher Burkhard, Van Ginderachter Jo A, Greter Melanie, Movahedi Kiavash
Аннотация
Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype, including a CLEC7Ahigh myelin-associated subset in the ME, shaped by ageing and metabolism. CVO microglia were ontogenically diverse: fetal monocytes entered the CVOs perinatally and generated long-lived monocyte-derived microglia that fully adopted a yolk-sac-derived microglia identity. After depletion, CVO microglia were repopulated by local Sall1high cells but also by monocytes in the AP. Similarly, perivascular CVO border-associated macrophages displayed a distinct phenotype and origin. Our findings establish CVOs as specialized immune niches that shape local macrophages, reflecting the immune and metabolic demands of these environments.