4.8 Article

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

Journal

SCIENCE
Volume 373, Issue 6553, Pages 409-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abf7844

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Funding

  1. National Institutes of Health [AT010416, AG034113, AG057496]

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The meninges contain a pool of monocytes and neutrophils supplied by adjacent skull and vertebral bone marrow, rather than by the blood. Under pathological conditions, CNS-infiltrating myeloid cells can originate from the brain borders and have distinct transcriptional signatures from their blood-derived counterparts. Therefore, myeloid cells from adjacent bone marrow niches are strategically placed to supply innate immune cells under both homeostatic and pathological conditions.
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 mouse 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 a reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches that harness meningeal immune cells.

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