Musio Silvia, Costanza Massimo, Poliani Pietro Luigi, Fontana Elena, Cominelli Manuela, Abolafio Gabriella, Steinman Lawrence, Pedotti Rosetta
Department of Clinical Neuroscience (S.M., M. Costanza, R.P.), Foundation Neurological Institute IRCCS C. Besta, Milan; Department of Molecular and Translational Medicine (P.L.P., E.F., M. Cominelli), Pathology Unit, University of Brescia; Department of Experimental Oncology and Molecular Medicine (G.A.), Fondazione IRCCS "Istituto Nazionale dei Tumori," Milan, Italy; and Department of Neurology and Neurological Sciences (L.S.), Stanford University School of Medicine, CA.
Neurol Neuroimmunol Neuroinflamm. 2017 Apr 14;4(3):e342. doi: 10.1212/NXI.0000000000000342. eCollection 2017 May.
To investigate the effects of targeting the high-affinity receptor for immunoglobulin E (FcεRI), that plays a central role in allergic responses and is constitutively expressed on mast cells and basophils, in clinical disease and autoimmune T-cell response in experimental MS.
Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein 35-55. Anti-FcεRI α-chain antibody was administered intraperitoneally. CNS immunohistochemistry, flow cytometry analysis of immune cell populations, IgE and histamine serum concentration, immune cell proliferation, and cytokine measurement were performed. In BALB/c mice, EAE was induced by immunization with myelin proteolipid protein 185-206.
Treatment with anti-FcεRIα antibody resulted in exacerbation of EAE and increased CNS inflammation in C57BL/6 mice. Treated mice displayed long-lasting complete depletion of basophils in the blood stream and peripheral lymphoid organs and increased antigen-induced immune cell proliferation and production of interferon-γ, interleukin (IL)-17, IL-6, and granulocyte-macrophage colony-stimulating factor. In BALB/c mice, which are T-helper (Th) 2 prone and resistant to EAE, treatment with anti-FcεRIα antibody restored susceptibility to EAE.
Our observations that anti-FcεRIα antibody increases Th1 and Th17 responses against myelin antigen and exacerbates EAE suggest that FcεRI, basophils, and possibly other FcεRI-bearing cells that might be affected by this antibody play important roles in influencing the severity of CNS autoimmunity.
免疫球蛋白E高亲和力受体（FcεRI）在过敏反应中起核心作用，在肥大细胞和嗜碱性粒细胞上组成性表达，研究靶向该受体在实验性多发性硬化症（MS）的临床疾病和自身免疫性T细胞反应中的作用。
用髓鞘少突胶质细胞糖蛋白35 - 55免疫C57BL/6小鼠诱导实验性自身免疫性脑脊髓炎（EAE）。腹腔注射抗FcεRIα链抗体。进行中枢神经系统免疫组织化学、免疫细胞群体的流式细胞术分析、血清IgE和组胺浓度测定、免疫细胞增殖及细胞因子检测。在BALB/c小鼠中，用髓鞘蛋白脂蛋白185 - 206免疫诱导EAE。
抗FcεRIα抗体治疗导致C57BL/6小鼠EAE加重，中枢神经系统炎症增加。治疗小鼠的血流和外周淋巴器官中嗜碱性粒细胞长期完全耗竭，抗原诱导的免疫细胞增殖增加，干扰素-γ、白细胞介素（IL）-17、IL-6和粒细胞-巨噬细胞集落刺激因子产生增加。在倾向于T辅助（Th）2且对EAE有抵抗力的BALB/c小鼠中，抗FcεRIα抗体治疗恢复了对EAE的易感性。
我们观察到抗FcεRIα抗体增加针对髓鞘抗原的Th1和Th17反应并加重EAE，这表明FcεRI、嗜碱性粒细胞以及可能受该抗体影响的其他表达FcεRI的细胞在影响中枢神经系统自身免疫的严重程度方面起重要作用。
