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Cited by 152Barrier Structure and Function StudiesMultiple Sclerosis Research StudiesDrug Transport and Resistance Mechanisms

Endothelial Wnt/β-catenin signaling reduces immune cell infiltration in multiple sclerosis

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Lengfeld, Justin E., Lutz, Sarah E., Smith, Julian R., Diaconu, Claudiu, Scott, Cameron, Kofman, Sigal B., Choi, Claire, Walsh, Craig M. +3 more·2017·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1609905114PMC PMC5320985
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Abstract

Significance: Endothelial cells (ECs) in the CNS form a unique blood–brain barrier (BBB) that is broken down in multiple sclerosis (MS). New therapies are sorely needed to restore BBB function in this disease. The wingless integrated MMTV (Wnt)/β-catenin pathway, which is essential for barrier formation, is activated in CNS ECs in MS and the animal model experimental autoimmune encephalomyelitis. When this pathway is inhibited in ECs before disease onset, mice develop more severe disease, with more immune cells entering the CNS owing to increased levels of proteins that promote interactions of immune cells with blood vessels and transport across vessels. Our findings suggest that pharmacologic enhancement of Wnt signaling may be helpful to limit BBB damage and CNS immune cell infiltration in MS.

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Authors
Lengfeld, J. E., Lutz, S. E., Smith, J. R., Diaconu, C., Scott, C., Kofman, S. B., Choi, C., Walsh, C. M., Raine, C. S., Agalliu, I., & Agalliu, D.
Affiliations
  • University of California, Irvine (US)
  • Columbia University Irving Medical Center (US)
  • Albert Einstein College of Medicine (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2017-01-30
Volume
114
Issue
7
Pages
E1168-E1177
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1609905114
PMC
PMC5320985
OpenAlex
W2580746852
Cited by
152
References
6
Citations by year
2026: 10 · 2025: 19 · 2024: 30 · 2023: 14 · 2022: 19 · 2021: 15 · 2020: 13 · 2019: 14 · 2018: 12 · 2017: 6
FWCI
6.14
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 181 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • HHS | NIH | National Heart, Lung, and Blood Institute (HL116995-01)
  • HHS | NIH | National Institute of Mental Health (MH109987-01A1)
  • National Multiple Sclerosis Society (RG4673A1/1, FG2035-A-1, CA1058-A-8, RG1001-K11)
  • California Institute for Regenerative Medicine (TR3-05603)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
multiple sclerosis, endothelial cells, Wnt/β-catenin signaling, blood-brain barrier, immune cell infiltration, experimental autoimmune encephalomyelitis, barrier function
MeSH terms
Animals, Blood-Brain Barrier, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis, CD4-Positive T-Lymphocytes, Mice, Congenic, Endothelial Cells, beta Catenin, Caveolin 1, Transcytosis, Wnt Signaling Pathway

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