An interesting emerging role for astrocytes in innate immunity is their participation in the formation of adventitial (perivascular) cuffs that harbor foci of activated immune cells [14, 32, 93]. Adventitial cuffing is emerging as important aspect of immune responses within host tissues across multiple organs as platforms for tissue resident immune memory and tertiary lymphoid organs [94]. In CNS, adventitial cuffing is well recognized in certain microbial infections and autoimmune inflammation, and astrocytes have long been recognized in borders around such perivascular cuffs in humans and experimental rodent models [1]. Transgenically targeted experimental disruption of astrocyte border formation leads to spread of inflammatory cells away from perivascular cuffs into the neural parenchyma resulting in loss of neural tissue in mice [14, 32]. Mechanistically, astrocyte processes form tight junctions via proteins claudin 1 and 4, which restrict or corral immune cells within the perivascular space when blood-borne leukocytes cross the endothelial BBB to gain entry into perivascular spaces in human co-culture models [93]. Astrocytes can also produce multiple cytokines and chemokines capable of recruiting and instructing lymphocytes, suggesting that astrocyte borders
