Decoding brain border immunity to enable future therapeutic avenues

The brain is no longer viewed as immunologically isolated but as an organ surrounded by dynamic border compartments that coordinate surveillance, drainage, and communication with the periphery. Key interfaces - including the meninges, blood-brain barrier, choroid plexus (ChP), and skull bone marrow - host specialized immune niches that regulate antigen sampling, leukocyte trafficking, and neuroimmune signaling. Recent advances in imaging and in single-cell and spatial profiling have revealed previously unrecognized cell types, migration routes, and barrier specializations that shape central nervous system (CNS) immunity in health and disease. Understanding how these border tissues sense, integrate, and modulate immune activity opens opportunities for therapeutically tuning neuroimmune responses at the brain's periphery while preserving parenchymal integrity.