Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation
Year: 2017
Type: article
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.
Source: Cell Reports
Authors: Sarah E. Lutz, Julian R. Smith, Dae Hwan Kim, Carl V.L. Olson, Kyle Ellefsen, Jennifer M. Bates, Sunil P. Gandhi, Dritan Agalliu
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Multiple Sclerosis Society, University of Arizona Cancer Center, Multiple Sclerosis Society, Fondation Leducq, National Institutes of Health, University of California, Irvine, National Heart, Lung, and Blood Institute, National Institute of Mental Health, NIH Office of the Director, National Cancer Institute, National Center for Research Resources
Awards: CNS angiogenesis and blood-brain barrier regulation by the Wnt inhibitor Apcdd1, G1556756270, G1605900718, G1913404079, Cellular and humoral immune mechanisms underlying neurovascular dysfunction in autoimmune encephalitis, G5025827294, Th17 cell-mediated CNS damage in response to recurrent S. pyogenes intranasal infections, Becton Dickinson LSR II Analytical Flow Cytometer, G9000088035, Cancer Center Support Grant
OpenAlex ID: W2768931384