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

Author:

Cugurra Andrea12ORCID,Mamuladze Tornike3ORCID,Rustenhoven Justin3ORCID,Dykstra Taitea3ORCID,Beroshvili Giorgi3,Greenberg Zev J.4ORCID,Baker Wendy2,Papadopoulos Zach35ORCID,Drieu Antoine3ORCID,Blackburn Susan3,Kanamori Mitsuhiro3,Brioschi Simone3ORCID,Herz Jasmin3,Schuettpelz Laura G.4,Colonna Marco3ORCID,Smirnov Igor3,Kipnis Jonathan1235ORCID

Affiliation:

1. Gutenberg Research Fellowship Group of Neuroimmunology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), 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.

Abstract

Getting around the blood–brain barrier The meninges comprise three membranes that surround and protect the central nervous system (CNS). Recent studies have noted the existence of myeloid cells resident there, but little is known about their ontogeny and function, and whether other meningeal immune cell populations have important roles remains unclear (see the Perspective by Nguyen and Kubes). Cugurra et al. found in mice that a large proportion of continuously replenished myeloid cells in the dura mater are not blood derived, but rather transit from cranial bone marrow through specialized channels. In models of CNS injury and neuroinflammation, the authors demonstrated that these myeloid cells have an immunoregulatory phenotype compared with their more inflammatory blood-derived counterparts. Similarly, Brioschi et al. show that the meninges host B cells that are also derived from skull bone marrow, mature locally, and likely acquire a tolerogenic phenotype. They further found that the brains of aging mice are infiltrated by a second population of age-associated B cells, which come from the periphery and may differentiate into autoantibody-secreting plasma cells after encountering CNS antigens. Together, these two studies may inform future treatment of neurological diseases. Science , abf7844, abf9277, this issue p. eabf7844 , p. eabf9277 ; see also abj8183, p. 396

Funder

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Institute of Neurological Disorders and Stroke

JK National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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