Pericytes regulate vascular immune homeostasis in the CNS.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_2E291B9300F3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pericytes regulate vascular immune homeostasis in the CNS.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Török O., Schreiner B., Schaffenrath J., Tsai H.C., Maheshwari U., Stifter S.A., Welsh C., Amorim A., Sridhar S., Utz S.G., Mildenberger W., Nassiri S., Delorenzi M., Aguzzi A., Han M.H., Greter M., Becher B., Keller A.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2021
Peer-reviewed
Oui
Volume
118
Numéro
10
Pages
e2016587118
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood-brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfb <sup>
ret/ret
</sup> ), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfb <sup>
ret/ret
</sup> mice inversely correlates with vessel pericyte coverage. Upon induction of experimental autoimmune encephalomyelitis (EAE), pericyte-deficient mice die of severe atypical EAE, which can be reversed with fingolimod, indicating that the mortality is due to the massive influx of immune cells into the brain. Additionally, administration of anti-VCAM-1 and anti-ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfb <sup>
ret/ret
</sup> mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation. Furthermore, we show that the presence of myelin peptide-specific peripheral T cells in Pdgfb <sup>
ret/ret
</sup> ;2D2 <sup>
tg
</sup> mice leads to the development of spontaneous neurological symptoms paralleled by the massive influx of leukocytes into the brain. These findings indicate that intrinsic changes within brain vasculature can promote the development of a neuroinflammatory disorder.
Mots-clé
MOG35–55–specific T cell receptor, autoimmune neuroinflammation, blood–brain barrier, leukocyte trafficking, pericyte
Pubmed
Open Access
Oui
Création de la notice
08/03/2021 13:13
Dernière modification de la notice
23/11/2022 7:09
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