Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice.
Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice.
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少突胶质细胞衍生的细胞外囊泡作为小鼠自身免疫性神经炎症的抗原特异性治疗。
DOI：
10.1126/scitranslmed.aba0599
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发表时间：
2020-11-04
影响因子：
17.1
通讯作者：
Rostami A
中科院分区：
文献类型：
--
作者：
Casella G;Rasouli J;Boehm A;Zhang W;Xiao D;Ishikawa LLW;Thome R;Li X;Hwang D;Porazzi P;Molugu S;Tang HY;Zhang GX;Ciric B;Rostami A
自身免疫性疾病，如多发性硬化症（MS）的发展，因为失败的外周免疫耐受的特定自身抗原（Ag）。许多方法的Ag特异性抑制自身免疫性神经炎症已被证明是有效的实验性自身免疫性脑脊髓炎（EAE），MS的动物模型。一个这样的方法是静脉内耐受诱导通过注射髓磷脂Ag用于触发EAE。然而，这种和类似的实验策略转化为MS的治疗受到MS患者中相关髓鞘Ag的不确定性的阻碍。为了解决这个问题，我们开发了一种依赖于少突胶质细胞（Ol）衍生的细胞外囊泡（Ol-EV）的治疗策略，所述细胞外囊泡天然含有多个髓鞘Ag。在几种EAE模型中，静脉内Ol-EV注射以髓磷脂Ag依赖性方式在药理学和治疗学上减少疾病病理生理学。治疗是安全的，并通过诱导免疫抑制性单核细胞和自身反应性CD4 + T细胞凋亡来恢复免疫耐受。此外，我们发现人Ols也释放含有最相关的髓鞘Ag的EV，为它们在MS治疗中的应用提供了基础。这些发现引入了一种以髓鞘Ag特异性方式抑制中枢神经系统（CNS）自身免疫的方法，而不需要鉴定靶Ag。
Autoimmune diseases such as multiple sclerosis (MS) develop because of failed peripheral immune tolerance for a specific self-antigen (Ag). Numerous approaches for Ag-specific suppression of autoimmune neuroinflammation have been proven effective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. One such approach is intravenous tolerance induction by injecting a myelin Ag used for triggering EAE. However, the translation of this and similar experimental strategies into therapy for MS has been hampered by uncertainty regarding relevant myelin Ags in MS patients. To address this issue, we developed a therapeutic strategy that relies on oligodendrocyte (Ol)-derived extracellular vesicles (Ol-EVs), which naturally contain multiple myelin Ags. Intravenous Ol-EV injection reduced disease pathophysiology in a myelin Ag-dependent manner, both prophylactically and therapeutically, in several EAE models. The treatment was safe and restored immune tolerance by inducing immunosuppressive monocytes and apoptosis of autoreactive CD4+ T cells. Furthermore, we showed that human Ols also released EVs containing most relevant myelin Ags, providing a basis for their use in MS therapy. These findings introduce an approach for suppressing central nervous system (CNS) autoimmunity in a myelin Ag-specific manner, without the need to identify the target Ag.
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影响因子：
32.4
作者：
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通讯作者：
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作者：
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通讯作者：
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