title: Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation.
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.
authors.affiliation: Neuroimmunology Unit, Center for the Study of Brain Diseases, Centre Hospitalier de l'Université de Montréal-Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada.
authors.forename: Hania
authors.initials: H
authors.lastname: Kebir
authors.forename: Katharina
authors.initials: K
authors.lastname: Kreymborg
authors.forename: Igal
authors.initials: I
authors.lastname: Ifergan
authors.forename: Aurore
authors.initials: A
authors.lastname: Dodelet-Devillers
authors.forename: Romain
authors.initials: R
authors.lastname: Cayrol
authors.forename: Monique
authors.initials: M
authors.lastname: Bernard
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giuliani
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002463:Cell Membrane Permeability; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D053804:Granzymes / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D018123:Receptors, Interleukin / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology*; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology