title: EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis.
abstract: The interaction between oxysterols and the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS), such as natalizumab. We previously showed that memory CD4+T lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-OHC) via EBI2 in the MS murine model experimental autoimmune encephalomyelitis. However, the EBI2 expression profile in human lymphocytes in both healthy and MS donors is unknown. Here, we characterize EBI2 biology in human lymphocytes. We observed that EBI2 is functionally expressed on memory CD4+T cells and is enhanced under natalizumab treatment. These data suggest a significant role for EBI2 in human CD4+T cell migration, notably in patients with MS. Better knowledge of EBI2 involvement in autoimmunity may therefore lead to an improved understanding of the physiopathology of MS.
authors.affiliation: Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland; Department of Pathology and Immunology, Geneva University Medical Center, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland; Division of Immunology and Allergology, Department of Medical Specialties, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
authors.forename: Aurélie S
authors.initials: AS
authors.lastname: Clottu
authors.affiliation: Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Mathias
authors.affiliation: Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Forum 1, 4002 Basel, Switzerland.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sailer
authors.affiliation: Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.affiliation: Division of Immunology and Allergology, Department of Medical Specialties, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Seebach
authors.affiliation: Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland; Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
authors.forename: Renaud
authors.initials: R
authors.lastname: Du Pasquier
authors.affiliation: Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland; Department of Pathology and Immunology, Geneva University Medical Center, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland; Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: caroline.pot-kreis@chuv.ch.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pot
mesh_terms: D000328:Adult; D018845:CD11 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000069442:Natalizumab / Q000494:pharmacology / Q000627:therapeutic use*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D018845:CD11 Antigens; C080105:GPR183 protein, human; D006888:Hydroxycholesterols; D000069442:Natalizumab; D043562:Receptors, G-Protein-Coupled; C057657:7,25-dihydroxycholesterol
keywords: G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2); lymphocyte trafficking; multiple sclerosis; natalizumab; oxysterols