A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis

doi:10.1126/science.aay3638

GSTDTAP > 气候变化

DOI	10.1126/science.aay3638
	A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
	Christina Krienke; Laura Kolb; Elif Diken; Michael Streuber; Sarah Kirchhoff; Thomas Bukur; Özlem Akilli-Öztürk; Lena M. Kranz; Hendrik Berger; Jutta Petschenka; Mustafa Diken; Sebastian Kreiter; Nir Yogev; Ari Waisman; Katalin Karikó; Özlem Türeci; Ugur Sahin
	2021-01-08
发表期刊	Science
出版年	2021
英文摘要	Autoimmune diseases, such as multiple sclerosis (MS), result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. Current treatments can cause systemic immune suppression and side effects such as increased risk of infections. Krienke et al. designed a messenger RNA vaccine strategy that lacks adjuvant activity and delivers MS autoantigens into lymphoid dendritic cells. This approach expands a distinct type of antigen-specific effector regulatory T cell that suppresses autoreactivity against targeted autoantigens and promotes bystander suppression of autoreactive T cells against other myelin-specific autoantigens. In mouse models of MS, the vaccine delayed the onset and reduced the severity of established disease without showing overt symptoms of general immune suppression. Science , this issue p. [145][1] 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 (m1Ψ 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 m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg cell) populations. Notably, these Treg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens. [1]: /lookup/doi/10.1126/science.aay3638
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/310442
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Christina Krienke,Laura Kolb,Elif Diken,et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis[J]. Science,2021.
APA	Christina Krienke.,Laura Kolb.,Elif Diken.,Michael Streuber.,Sarah Kirchhoff.,...&Ugur Sahin.(2021).A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis.Science.
MLA	Christina Krienke,et al."A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis".Science (2021).