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dc.contributor.author
Török, Orsolya
dc.contributor.author
Schreiner, Bettina
dc.contributor.author
Schaffenrath, Johanna
dc.contributor.author
Tsai, Hsing-Chuan
dc.contributor.author
Maheshwari, Upasana
dc.contributor.author
Stifter, Sebastian A.
dc.contributor.author
Welsh, Christina
dc.contributor.author
Amorim, Ana
dc.contributor.author
Sridhar, Sucheta
dc.contributor.author
Utz, Sebastian G.
dc.contributor.author
Mildenberger, Wiebke
dc.contributor.author
Nassiri, Sina
dc.contributor.author
Delorenzi, Mauro
dc.contributor.author
Aguzzi, Adriano
dc.contributor.author
Han, May H.
dc.contributor.author
Greter, Melanie
dc.contributor.author
Becher, Burkhard
dc.contributor.author
Keller, Annika
dc.date.accessioned
2021-03-24T14:07:03Z
dc.date.available
2021-03-18T04:37:33Z
dc.date.available
2021-03-24T14:07:03Z
dc.date.issued
2021-03-09
dc.identifier.issn
0027-8424
dc.identifier.issn
1091-6490
dc.identifier.other
10.1073/pnas.2016587118
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/475206
dc.identifier.doi
10.3929/ethz-b-000475206
dc.description.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 (Pdgfbret/ret), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfbret/ret 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 Pdgfbret/ret 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 Pdgfbret/ret;2D2tg 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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
National Academy of Sciences
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
pericyte
en_US
dc.subject
blood–brain barrier
en_US
dc.subject
leukocyte trafficking
en_US
dc.subject
autoimmune neuroinflammation
en_US
dc.subject
MOG35–55–specific T cell receptor
en_US
dc.title
Pericytes regulate vascular immune homeostasis in the CNS
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2021-03-02
ethz.journal.title
Proceedings of the National Academy of Sciences of the United States of America
ethz.journal.volume
118
en_US
ethz.journal.issue
10
en_US
ethz.journal.abbreviated
Proc Natl Acad Sci U S A
ethz.pages.start
e2016587118
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2021-03-18T04:38:01Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-03-24T14:07:17Z
ethz.rosetta.lastUpdated
2022-03-29T05:58:16Z
ethz.rosetta.versionExported
true
ethz.COinS
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