The segregation and limited regenerative capacity of the CNS necessitate a specialized and tightly regulated resident immune system that continuously guards the CNS against invading pathogens and injury. Immunity in the CNS has generally been attributed to neuron-associated microglia in the parenchyma, whose origin and functions have recently been elucidated. However, there are several other specialized macrophage populations at the CNS borders, including dural, leptomeningeal, perivascular and choroid plexus macrophages (collectively known as CNS-associated macrophages (CAMs)), whose origins and roles in health and disease have remained largely uncharted. CAMs are thought to be involved in regulating the fine balance between the proper segregation of the CNS, on the one hand, and the essential exchange between the CNS parenchyma and the periphery, on the other. Recent studies that have been empowered by major technological advances have shed new light on these cells and suggest central roles for CAMs in CNS physiology and in the pathogenesis of diseases.
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