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EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis.

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. Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Forum 1, 4002 Basel, Switzerland. Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Division of Immunology and Allergology, Department of Medical Specialties, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. 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. 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.

Cell reports. 2017;(1):213-224
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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.