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Skull bone marrow channels as immune gateways to the central nervous system

Nature Neuroscience volume 26, pages 2052–2062 (2023)Cite this article

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Abstract

Decades of research have characterized diverse immune cells surveilling the CNS. More recently, the discovery of osseous channels (so-called ‘skull channels’) connecting the meninges with the skull and vertebral bone marrow has revealed a new layer of complexity in our understanding of neuroimmune interactions. Here we discuss our current understanding of skull and vertebral bone marrow anatomy, its contribution of leukocytes to the meninges, and its surveillance of the CNS. We explore the role of this hematopoietic output on CNS health, focusing on the supply of immune cells during health and disease.

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Fig. 1: Immune landscape at the outer borders of the central nervous system.
Fig. 2: Skull and vertebral channels are bidirectional conduits.
Fig. 3: Skull bone marrow responds to central nervous system perturbations.

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Acknowledgements

This work was funded in part by US federal funds from the National Institutes of Health (NS108419, NS127808, HL139598, HL142494, AT010416 and NS096967), a Cure Alzheimer’s Fund grant (Berg Brain Entry and Exit Consortium) and the BJC HealthCare Investigators Program.

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  1. These authors contributed equally: Jose A. Mazzitelli, Fadi E. Pulous.

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    Jose A. Mazzitelli, Leon C. D. Smyth & Jonathan Kipnis

  2. Center for Brain Immunology and Glia (BIG), Washington University School of Medicine, St. Louis, MO, USA

    Jose A. Mazzitelli, Leon C. D. Smyth & Jonathan Kipnis

  3. Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, USA

    Jose A. Mazzitelli & Jonathan Kipnis

  4. Neuroscience Graduate Program, Washington University School of Medicine, St. Louis, MO, USA

    Jose A. Mazzitelli & Jonathan Kipnis

  5. Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Fadi E. Pulous, Zeynep Kaya, Michael A. Moskowitz & Matthias Nahrendorf

  6. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Fadi E. Pulous, Zeynep Kaya, Michael A. Moskowitz & Matthias Nahrendorf

  7. Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand

    Justin Rustenhoven

  8. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Michael A. Moskowitz

  9. Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Matthias Nahrendorf

  10. Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

    Matthias Nahrendorf

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Correspondence to Jonathan Kipnis or Matthias Nahrendorf.

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Competing interests

J.K. is a scientific advisor for Sana Biotechnology. M.N. has received funds or material research support from Alnylam, Biotronik, CSL Behring, GlycoMimetics, GSK, Medtronic, Novartis and Pfizer, as well as consulting fees from Biogen, Gimv, IFM Therapeutics, Molecular Imaging, Sigilon, Verseau Therapeutics and Bitterroot. The other authors declare no competing interests.

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Mazzitelli, J.A., Pulous, F.E., Smyth, L.C.D. et al. Skull bone marrow channels as immune gateways to the central nervous system. Nat Neurosci 26, 2052–2062 (2023). https://doi.org/10.1038/s41593-023-01487-1

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