The dura mater: A hub for immune surveillance at the central nervous system borders

The outer layer of the meninges, the dura mater, forms a critical interface at the border of the central nervous system (CNS). While historically the dura was viewed as a protective physical barrier for the brain and spinal cord, providing structural support for the venous sinuses, more recent research has shown that it is intimately connected to adjacent bones, CNS organs, the systemic circulation, and peripheral organs, particularly the gastrointestinal tract, via immune cell immigrants. In parallel, advances in immunophenotyping have revealed that the dura houses a plethora of immune cells, some within aggregates in dural-associated lymphoid tissue that can support the activation of adaptive immune cells, including germinal center responses. These dural immune cells can acquire immunological information from the network of dural blood and lymphatic vessels, as well as autonomic and sensory nerves, and newly discovered arachnoid cuff entry points provide a direct connection with the subarachnoid space. In this review, we will summarize recent evidence that highlights the dura as a hub for the detection, integration, and relay of immune signals from outside and inside the CNS.