A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
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DOI：
10.1126/science.aay3638
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发表时间：
2021-01-08
期刊：
影响因子：
56.9
通讯作者：
Sahin, Ugur
中科院分区：
文献类型：
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作者：
Krienke, Christina;Kolb, Laura;Sahin, Ugur
能够在不引起全身免疫抑制的情况下控制自身反应性T细胞是治疗自身免疫性疾病的主要目标。关键的挑战是在非炎症性环境中安全和有效地传递药物上明确定义的抗原。在这里，我们发现，在没有共刺激信号的情况下，系统地递送编码疾病相关自身抗原的纳米颗粒配方的1甲基假尿苷修饰的信使RNA(M1 Psi MRNA)导致抗原递呈到脾CD11c(+)抗原提呈细胞上。在几种多发性硬化症的小鼠模型中，这种M1Psi mRNA的治疗可以抑制这种疾病。治疗效果与效应性T细胞的减少和调节性T细胞(T-reg细胞)群体的发展有关。值得注意的是，这些T-reg细胞执行强大的旁观者免疫抑制，从而改善由同源和非同源自身抗原诱导的疾病。
The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1 Psi mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c(+) antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1 Psi mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (T-reg cell) populations. Notably, these T-reg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.