Mural cells interact with macrophages in the dura mater to regulate CNS immune surveillance

The central nervous system (CNS) tightly regulates access of circulating immune cells. Immunosurveillance is therefore managed in the meninges at the borders of the CNS. Here, we demonstrated that mural cells, which include pericytes and smooth muscle cells, decreased coverage around blood vessels in the dura, the outermost layer of the meninges, and upregulated gene pathways involved in leukocyte migration in presymptomatic experimental autoimmune encephalomyelitis (EAE). Partially depleting mural cells promoted the trafficking of CNS antigen-specific T cells to the dura in a process that depended on resident antigen-presenting cells, thereby increasing susceptibility to passive EAE. Mechanistically, mural cells physically contacted macrophages in the dura and transferred cytoplasmic components, including processing bodies (RNA granules shown to reprogram transcriptomes), which were critical to suppress antigen-dependent T helper (TH) cell activation and TH17 differentiation. Our study revealed a mechanism by which mural cell-macrophage interactions regulate the trafficking of CNS antigen-specific T cells to the dura.