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.
Cell Rep. 2017 Jan 3;18(1):213-224. doi: 10.1016/j.celrep.2016.12.006.
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.
氧化固醇与 G 蛋白偶联受体 Epstein-Barr 病毒诱导基因 2（EBI2）的相互作用可精细调节免疫细胞的迁移，这一机制是几种治疗多发性硬化症（MS）的疾病修正治疗药物的有效靶点，例如那他珠单抗。我们之前曾表明，在 MS 实验性自身免疫性脑脊髓炎的小鼠模型中，记忆性 CD4 T 淋巴细胞通过 EBI2 特异性地对 7α,25-二羟胆固醇（7α,25-OHC）作出反应。然而，在健康供体和 MS 供体的人类淋巴细胞中，EBI2 的表达谱尚不清楚。在这里，我们对人类淋巴细胞中的 EBI2 生物学进行了描述。我们观察到 EBI2 在记忆性 CD4 T 细胞上具有功能性表达，并在那他珠单抗治疗下增强。这些数据表明 EBI2 在人类 CD4 T 细胞迁移中具有重要作用，尤其是在 MS 患者中。因此，对 EBI2 在自身免疫中的作用的更好理解可能会促进对 MS 病理生理学的深入了解。
