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Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation.

Authors
  • Lutz, Sarah E1
  • Smith, Julian R2
  • Kim, Dae Hwan3
  • Olson, Carl V L3
  • Ellefsen, Kyle3
  • Bates, Jennifer M4
  • Gandhi, Sunil P3
  • Agalliu, Dritan5
  • 1 Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: [email protected]
  • 2 Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
  • 3 Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA.
  • 4 Institute for Immunology, University of California, Irvine, Irvine, CA 92697, USA.
  • 5 Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA; Columbia Translational Neuroscience Initiative, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Nov 21, 2017
Volume
21
Issue
8
Pages
2104–2117
Identifiers
DOI: 10.1016/j.celrep.2017.10.094
PMID: 29166603
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs) or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB) before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. We find that dynamic tight junction remodeling occurs early in EAE but does not depend upon caveolar transport. Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry into the CNS. Moreover, therapies that target both tight junction degradation and caveolar transcytosis may limit lymphocyte infiltration during inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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