Border-associated macrophages as gatekeepers of brain homeostasis and immunity

The brain’s border tissues serve as essential hubs for neuroimmune regulation and the trafficking of biomaterials to and from the brain. These complex tissues—including the meninges, perivascular spaces, choroid plexus, and circumventricular organs—balance the brain’s need for immune privilege with immune surveillance and blood-brain communication. Macrophages are integral components of these tissues, taking up key strategic positions within the brain’s circulatory system. These border-associated macrophages, or “BAMs,” are therefore emerging as pivotal for brain homeostasis and disease. BAMs perform trophic functions that help to support border homeostasis but also act as immune sentinels essential for border defense. In this review, we integrate recent findings on BAM origins, cell states, and functions, aiming to provide global insights and perspectives on the complex relationship between these macrophages and their border niche.