Pericytes regulate vascular immune homeostasis in the CNS.

Details

Serval ID
serval:BIB_2E291B9300F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pericytes regulate vascular immune homeostasis in the CNS.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(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
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
118
Number
10
Pages
e2016587118
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
MOG35–55–specific T cell receptor, autoimmune neuroinflammation, blood–brain barrier, leukocyte trafficking, pericyte
Pubmed
Open Access
Yes
Create date
08/03/2021 14:13
Last modification date
11/12/2021 7:38
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