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

  • Science. 2021 Jul 23;373(6553):eabf7844. doi: 10.1126/science.abf7844.
Andrea Cugurra  #  1  2 ,  Tornike Mamuladze  #  3 ,  Justin Rustenhoven  #  3 ,  Taitea Dykstra  3 ,  Giorgi Beroshvili  3 ,  Zev J Greenberg  4 ,  Wendy Baker  2 ,  Zach Papadopoulos  3  5 ,  Antoine Drieu  3 ,  Susan Blackburn  3 ,  Mitsuhiro Kanamori  3 ,  Simone Brioschi  3 ,  Jasmin Herz  3 ,  Laura G Schuettpelz  4 ,  Marco Colonna  3 ,  Igor Smirnov  3 ,  Jonathan Kipnis  6  2  3  5
Affiliations
  • 1. Gutenberg Research Fellowship Group of Neuroimmunology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • 2. Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA, USA.
  • 3. Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.
  • 4. Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA.
  • 5. Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • 6. Gutenberg Research Fellowship Group of Neuroimmunology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. [email protected].
  • # Contributed equally.
PMID: 34083447 DOI: 10.1126/science.abf7844
Abstract

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.