1. EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis
- Author
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Amandine Mathias, Andreas W. Sailer, Renaud Du Pasquier, Caroline Pot, Aurélie Sarah Clottu, Jorg Dieter Seebach, and Myriam Schluep
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,0301 basic medicine ,Multiple Sclerosis ,ddc:616.07 ,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 ,G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) ,lymphocyte trafficking ,multiple sclerosis ,natalizumab ,oxysterols ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Receptors, G-Protein-Coupled ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Natalizumab ,Cell Movement ,medicine ,Receptor ,Gene ,ddc:616 ,CD11 Antigens ,business.industry ,Mechanism (biology) ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,medicine.disease ,Hydroxycholesterols ,Pathophysiology ,3. Good health ,030104 developmental biology ,Immunology ,business ,Immunologic Memory ,030217 neurology & neurosurgery ,medicine.drug - 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.
- Published
- 2017
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