Skull bone marrow immunity in brain health and disease: mechanisms and models

The skull bone marrow (sBM) is a hematopoietic site intimately connected to the dura mater-the outermost layer of the meninges that surround the central nervous system (CNS)-via vascular channels that enable trafficking of immune cells and sampling of cerebrospinal fluid. sBM-derived cells directly access the dura under homeostasis and, following pathology, can infiltrate the CNS, contributing to immune surveillance, neuroinflammation, and disease outcomes. Here, we discuss the anatomical and functional properties of the sBM and critically evaluate the various approaches used to study its role in neuroimmune interactions. We also assess the translational potential of these findings in humans, highlighting promising avenues and current limitations for therapeutic targeting. While current approaches to specifically manipulate the sBM have limitations, its close relationship with the CNS underscores its potential as a novel treatment target. Continued methodological refinement and cross-species validation will be essential to harness the sBM for treating neurological disorders.