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Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma

Cugurra, A;Mamuladze, T;Rustenhoven, J;Dykstra, T;Beroshvili, G;Greenberg, ZJ;Baker, W;Papadopoulos, Z;Drieu, A;Blackburn, S;Kanamori, M;Brioschi, S;Herz, J;Schuettpelz, LG;Colonna, M;Smirnov, I;Kipnis, J;

The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the meninges contain a pool of monocytes and neutrophils supplied not from the blood, but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation, CNS-infiltrating myeloid cells can originate from brain borders and display transcriptional signatures distinct from their blood-derived counterparts. Thus, CNS borders are populated by myeloid cells from adjacent bone-marrow niches, strategically placed to supply innate immune cells under homeostatic and pathological conditions. These findings call for reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches harnessing meningeal immune cells.