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

Andrea Cugurra(Johannes Gutenberg University Mainz), Tornike Mamuladze(Washington University in St. Louis), Justin Rustenhoven(Washington University in St. Louis), Taitea Dykstra(Washington University in St. Louis), Giorgi Beroshvili(Washington University in St. Louis), Zev J. Greenberg(Washington University in St. Louis), Wendy Baker(University of Virginia), Zachary Papadopoulos(Washington University in St. Louis), Antoine Drieu(Washington University in St. Louis), Susan Blackburn(Washington University in St. Louis), Mitsuhiro Kanamori(Washington University in St. Louis), Simone Brioschi(Washington University in St. Louis), Jasmin Herz(Washington University in St. Louis), Laura G. Schuettpelz(Washington University in St. Louis), Marco Colonna(Washington University in St. Louis), Igor Smirnov(Washington University in St. Louis), Jonathan Kipnis(Johannes Gutenberg University Mainz)
Science
June 3, 2021
Cited by 621Open Access
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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


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