ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms.

ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms.
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表达 MOG 的 ESC 衍生胸腺上皮细胞通过中枢和外周耐受机制预防 EAE

DOI:
10.1016/j.cellimm.2017.10.007
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发表时间:
2017-12
影响因子:
4.3
通讯作者:
Lai L
Lai L
中科院分区:
医学4区
文献类型:
--
作者:
Su M;Lin Y;Cui C;Tian X;Lu X;He Z;Lai L

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实验性自身免疫性脑脊髓炎 (EAE) 是多发性硬化症 (MS) 的动物模型,通过使用致病自身抗原(例如髓磷脂少突胶质细胞糖蛋白 (MOG))进行免疫诱导。我们之前曾报道,移植来自 129S6SvEv Tac 小鼠胚胎干细胞 (mESC) 的表达胸腺上皮祖细胞 (TEP) 的 MOG 可阻止 EAE 的发展。在这项研究中,我们扩展了之前的研究,表明移植来自 C57BL/6 小鼠的表达 mESC-TEP 的 MOG 也可以预防 EAE 的发展。此外,通过使用 MOG 特异性 T 细胞受体 (TCR) 转基因小鼠模型,我们证明中枢和外周耐受都参与预防表达 MOG 的 mESC-TEP 诱导的 EAE。我们的结果表明,移植表达MOG的人ESC-TEP可能为诱导MOG特异性免疫耐受提供有效的方法,从而预防和治疗MS。
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), and is induced by immunization with disease-causative self-antigens such as myelin oligodendrocyte glycoprotein (MOG). We have previously reported that transplantation of MOG expressing thymic epithelial progenitors (TEPs) derived from 129S6SvEv Tac mouse embryonic stem cells (mESCs) prevented the development of EAE. In this study, we expand our previous studies to show that transplantation of MOG expressing mESC-TEPs derived from C57BL/6 mice also prevents EAE development. Furthermore, by using a MOG-specific T cell receptor (TCR) transgenic mouse model, we demonstrate that both central and peripheral tolerances are involved in the prevention of EAE induced by MOG expressing mESC-TEPs. Our results suggest that transplantation of human ESC-TEPs expressing MOG may provide an effective approach for the induction of MOG-specific immune tolerance, thereby the prevention and treatment of MS.
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