title: EphrinB1 and EphrinB2 regulate T cell chemotaxis and migration in experimental autoimmune encephalomyelitis and multiple sclerosis.
abstract: T cells are believed to be key effector cells in multiple sclerosis (MS). In this study, we examined the roles of T cell ephrinB1 (EFNB1) and ephrinB2 (EFNB2) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and MS. We provide evidence that animals with T cell specific double deletion of EFNB1 and EFNB2 (dKO) have reduced proliferation in response to MOG35-55, defective Th1 and Th17 differentiations and significantly lower scores of MOG-induced EAE. We further demonstrate that dKO T cells are compromised in their ability to migrate into the CNS of EAE animals in vivo and towards multiple chemokines in vitro. Using deletion mutations, we identified a critical 11-aa EFNB1 intracellular domain segment that controls T cell chemotaxis towards CCL21. In humans, EFNB1 and EFNB2 are highly expressed in Th1 and Th17 cells and EFNB1- and EFNB2-expressing T cells are found among immune cell infiltrates in MS lesions. Reverse signaling through EFNB1 and EFNB2 in human Th17 cells enhances their migration through a monolayer of blood brain barrier endothelial cells. Our study demonstrates that expression of EFNB1 and EFNB2 is implicated in Th cell differentiation and migration to inflammatory sites in both EAE and MS.
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Department of Neuroscience, Faculty of Medicine, Université de Montréal, 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Hasselt University, Biomedical Research Institute and transnationale Universiteit Limburg, School of Life Sciences, Agoralaan building C, 3590 Diepenbeek, Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Broux
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Department of Neuroscience, Faculty of Medicine, Université de Montréal, 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Soufiane
authors.initials: S
authors.lastname: Ghannam
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Department of Neuroscience, Faculty of Medicine, Université de Montréal, 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Larochelle
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Department of Neuroscience, Faculty of Medicine, Université de Montréal, 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada. Electronic address: a.prat@umontreal.ca.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: The Research Center of the University of Montreal Hospital Center e (CRCHUM), 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada; Division of Nephrology, Department of Medicine, Faculty of Medicine, Université de Montréal, 900 Rue Saint-Denis, Montréal H2X 0A9, Québec, Canada. Electronic address: jianping.wu@umontreal.ca.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D036387:Ephrin-B1 / Q000378:metabolism*; D036388:Ephrin-B2 / Q000378:metabolism*; D005260:Female; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C484288:EFNB1 protein, human; C000601239:EFNB2 protein, human; C000601240:EFNB2 protein, mouse; C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D036388:Ephrin-B2
keywords: Central nervous system; Ephrins; Experimental autoimmune encephalomyelitis; Migration; Multiple sclerosis; T helper cells