Skull channels as gateways for immune surveillance of the brain.

The central nervous system (CNS), once considered immune privileged, is, in fact, protected by a dynamic immune compartment located in the meninges. These immune cells are crucial for brain protection, controlling neuroinflammation, and also supporting neural function. Recent studies show that meningeal immune cells, including myeloid and B cells, partly originate from the skull bone marrow, which communicates directly with the meninges via specialized skull channels identified in mice and humans. These channels allow immune cell trafficking and cerebrospinal fluid (CSF) exchange, positioning the skull marrow as a CSF-sensing niche. Therefore, understanding skull-meninges-brain interactions reveals a functional connection between the skull marrow and the CNS, offering new insights into neuroimmune regulation and potential therapeutic strategies in neuroinflammatory conditions.