Reimagining the meninges from a neuroimmune perspective: a boundary, but not peripheral.

Abstract

Recent advances in neuroscience have transformed our understanding of the meninges, the layers surrounding the central nervous system (CNS). Two key findings have advanced our understanding: researchers identified cranial bone marrow as a reservoir for meningeal immune cells, and rediscovered a brain lymphatic system. Once viewed merely as a protective barrier, the meninges are now recognized as a dynamic interface crucial for neuroimmune interactions. This shift in perspective highlights their unique role in maintaining CNS balance, shaping brain development, and regulating responses to injury and disease. This review synthesizes the latest insights into meningeal anatomy and function, with a focus on newly identified structures such as dural-associated lymphoid tissues (DALT) and arachnoid cuff exit (ACE) points. We also examine the diverse immune cell populations within the meninges and their interactions with the CNS, underscoring the emerging view of the meninges as active participants in brain immunity. Finally, we outline critical unanswered questions about meningeal immunity, proposing directions for future research. By addressing these knowledge gaps, we aim to deepen our understanding of the meninges' role in brain health and disease, potentially paving the way for novel therapeutic approaches.