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

Aurélie S Clottu; Amandine Mathias; Andreas W Sailer; Myriam Schluep; Jörg D Seebach; Renaud Du Pasquier; Caroline Pot

doi:10.1016/j.celrep.2016.12.006

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

Cell Rep. 2017 Jan 3;18(1):213-224. doi: 10.1016/j.celrep.2016.12.006.

Authors

Aurélie S Clottu¹, Amandine Mathias², Andreas W Sailer³, Myriam Schluep⁴, Jörg D Seebach⁵, Renaud Du Pasquier⁶, Caroline Pot⁷

Affiliations

¹ 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.
² Laboratories of Neuroimmunology, Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
³ Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Forum 1, 4002 Basel, Switzerland.
⁴ Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
⁵ Division of Immunology and Allergology, Department of Medical Specialties, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
⁶ 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.
⁷ 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.

PMID: 28052250
DOI: 10.1016/j.celrep.2016.12.006

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.

Keywords: G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2); lymphocyte trafficking; multiple sclerosis; natalizumab; oxysterols.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD11 Antigens / metabolism
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / metabolism*
Cell Movement / drug effects
Humans
Hydroxycholesterols / pharmacology
Immunologic Memory* / drug effects
Multiple Sclerosis / immunology*
Multiple Sclerosis / metabolism*
Multiple Sclerosis / pathology
Natalizumab / pharmacology
Natalizumab / therapeutic use*
Receptors, G-Protein-Coupled / metabolism*

Substances

CD11 Antigens
GPR183 protein, human
Hydroxycholesterols
Natalizumab
Receptors, G-Protein-Coupled
7,25-dihydroxycholesterol