Abstract
T(H)17 lymphocytes appear to be essential in the pathogenesis of numerous inflammatory diseases. We demonstrate here the expression of IL-17 and IL-22 receptors on blood-brain barrier endothelial cells (BBB-ECs) in multiple sclerosis lesions, and show that IL-17 and IL-22 disrupt BBB tight junctions in vitro and in vivo. Furthermore, T(H)17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4+ lymphocyte recruitment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blood-Brain Barrier / drug effects
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Blood-Brain Barrier / immunology*
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CD4-Positive T-Lymphocytes / immunology
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Case-Control Studies
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Cell Membrane Permeability
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Cell Movement / immunology
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Cells, Cultured
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Central Nervous System / physiopathology*
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Dose-Response Relationship, Drug
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Endothelial Cells / immunology
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Endothelial Cells / metabolism
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Endothelium, Vascular / immunology
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Endothelium, Vascular / metabolism
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Granzymes / immunology
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Humans
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Inflammation / etiology
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Inflammation / physiopathology*
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Interleukin-17 / immunology
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Interleukin-17 / pharmacology
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Multiple Sclerosis / immunology
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Multiple Sclerosis / pathology
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Receptors, Interleukin / immunology
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T-Lymphocytes, Helper-Inducer / enzymology
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T-Lymphocytes, Helper-Inducer / immunology*
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Tight Junctions / metabolism
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Tight Junctions / pathology
Substances
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Interleukin-17
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Receptors, Interleukin
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interleukin-22 receptor
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Granzymes