ApoE缺乏可保护代谢应激下注射部位mRNA疫苗诱导的线粒体功能障碍。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI:10.7150/thno.119545
Sun-Hee Cho, Byeongkwon Choi, Jisun Lee, Yu-Sun Lee, Mi-Ock Baek, You-Jeung Lee, Chae-Ok Gil, Min-Kyung Choi, Sana Abdul Khaliq, Syeda Maham, Jae-Kyung Hyun, Gahyun Roh, Huijeong Choi, Sowon Lee, Seo-Hyeon Bae, Seonghyun Lee, Hyo-Jung Park, Jae-Hun Ahn, Na-Young Lee, Byeong-Cheol Kang, Young Kyo Seo, Byung-Kwan Lim, Jae-Hwan Nam, Mina Rho, Mee-Sup Yoon
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引用次数: 0

摘要

理由:mRNA疫苗接种的局部组织效应仍不完全清楚。我们研究了在不同代谢状态和载脂蛋白E (ApoE)状态下,接种SARS-CoV-2 mRNA对注射部位组织的影响。方法:我们在常规饮食和高脂肪饮食下对野生型和apoe缺陷小鼠以及猕猴进行肌肉注射SARS-CoV-2 mRNA疫苗接种。我们进行了转录组学分析、超微结构检查、包括握力测试在内的功能评估和免疫评估,以表征局部和全身反应。结果:在野生型动物中,肌肉注射疫苗引起局部损伤,其特征是炎症、线粒体破坏和握力降低。转录组学和超微结构分析揭示了去神经相关的变化,线粒体基因下调,嵴破坏以及免疫和凋亡途径的激活。apoe缺陷小鼠,特别是在西方饮食条件下,显示出线粒体和炎症反应的保护作用,尽管疫苗表达水平相当。这种保护包括减轻线粒体基因下调,保持线粒体DNA完整性,减少炎症反应。虽然ApoE缺乏导致抗体产生减少,但T细胞反应保持完整,表明选择性免疫调节。心脏组织显示最小的转录变化,证实了注射部位特异性作用。结论:ApoE缺乏对疫苗诱导的注射部位线粒体和炎症损伤具有保护作用,在代谢应激条件下具有增强的保护作用。这些发现揭示了代谢状态、脂质代谢和局部疫苗反应之间的重要相互作用,可能为不同患者群体的疫苗接种策略提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ApoE deficiency protects from mRNA vaccine-induced mitochondrial dysfunction at the injection site under metabolic stress.

Rationale: The local tissue effects of mRNA vaccination remain incompletely understood. We investigated how SARS-CoV-2 mRNA vaccination impacts injection site tissues in the context of different metabolic states and apolipoprotein E (ApoE) status. Methods: We administered intramuscular SARS-CoV-2 mRNA vaccination to wild-type and ApoE-deficient mice under regular and high-fat diets, as well as macaques. We performed transcriptomic analysis, ultrastructural examination, functional assessments including grip strength testing, and immunological evaluations to characterize local and systemic responses. Results: Intramuscular vaccination induced localized injury characterized by inflammation, mitochondrial disruption, and reduced grip strength in wild-type animals. Transcriptomic and ultrastructural analyses revealed denervation-associated changes, downregulation of mitochondrial genes, cristae disruption, and activation of immune and apoptotic pathways. ApoE-deficient mice, particularly under Western diet conditions, demonstrated protection from mitochondrial and inflammatory responses despite comparable vaccine expression levels. This protection involved attenuated mitochondrial gene downregulation, preserved mitochondrial DNA integrity, and reduced inflammatory responses. While ApoE deficiency resulted in diminished antibody production, T cell responses remained intact, indicating selective immunomodulation. Cardiac tissue showed minimal transcriptional changes, confirming injection site-specific effects. Conclusions: ApoE deficiency provides protection against vaccine-induced mitochondrial and inflammatory damage at the injection site, with enhanced protective effects under metabolic stress conditions. These findings reveal important interactions between metabolic status, lipid metabolism, and local vaccine responses that may inform vaccination strategies in different patient populations.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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