耐辐射球菌细胞外囊泡富集脱黄素驱动il -10依赖性树突状细胞耐受编程。

IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jeong Moo Han, Jaeyoon Lim, Woo Sik Kim, Bo-Gyeong Yoo, Jong-Hyun Jung, Sangyong Lim, Eui-Baek Byun
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引用次数: 0

摘要

来源于细菌的细胞外囊泡(EVs)正在成为影响宿主免疫的强有力的生物活性载体。耐辐射球菌是一种具有强抗氧化能力的嗜极细菌,其产生的ev富含去氧黄质(DX),这是一种具有活性氧清除活性的类胡萝卜素。在此,我们在生化实验中评估了D. radiodurans衍生的ev (r1 - ev)的抗氧化活性及其对树突状细胞(dc)的免疫调节作用。r1 - ev的抗氧化活性明显高于DX缺乏突变株的ev (ΔcrtI-EVs),与DX富集一致。在脂多糖存在的情况下,r1 - ev处理的骨髓源性dc显示表面成熟标志物和促炎细胞因子的表达减少,而白细胞介素-10 (IL-10)的产生和抗原摄取得到保留,表明耐受性表型。这种耐受性程序导致同种异体CD4+和CD8+ T细胞增殖和细胞因子产生减少。在机制上,r1 - ev抑制丝裂原活化蛋白激酶(MAPK)和核因子κB (NF-κB)信号通路,这是DC活化的关键调节因子。重要的是,IL-10中和逆转了这些效应,恢复了DC和T细胞的激活。值得注意的是,ΔcrtI-EVs的抗氧化和免疫调节活性较弱。总之,我们的研究结果确定r1 - ev是双重功能,DX-和il -10依赖的纳米平台,集成了抗氧化和耐受性,在炎症和自身免疫性疾病控制中具有潜在的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deinoxanthin-Enriched Extracellular Vesicles from Deinococcus radiodurans Drive IL-10-Dependent Tolerogenic Programming of Dendritic Cells.

Extracellular vesicles (EVs) derived from bacteria are emerging as potent bioactive carriers that affect host immunity. Deinococcus radiodurans, an extremophilic bacterium with strong antioxidant capacity, produces EVs enriched in deinoxanthin (DX), a carotenoid with a reactive oxygen species-scavenging activity. Here, we assessed the antioxidant activity of D. radiodurans-derived EVs (R1-EVs) in biochemical assays and their immunomodulatory effects on dendritic cells (DCs). R1-EVs exhibited significantly higher antioxidant activity than EVs from a DX-deficient mutant strain (ΔcrtI-EVs), consistent with DX enrichment. Bone marrow-derived DCs treated with R1-EVs in the presence of lipopolysaccharide displayed reduced expression of surface maturation markers and pro-inflammatory cytokines, while interleukin-10 (IL-10) production and antigen uptake were preserved, indicating a tolerogenic phenotype. This tolerogenic program led to decreased proliferation and cytokine production in allogeneic CD4+ and CD8+ T cells. Mechanistically, R1-EVs inhibited mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, key regulators of the DC activation. Importantly, IL-10 neutralization reversed these effects, restoring DC and T cell activation. Notably, ΔcrtI-EVs showed weaker antioxidant and immunoregulatory activities. Together, our findings identify R1-EVs as dual-functions, DX- and IL-10-dependent nanoplatform that integrates antioxidant and tolerogenic properties, with potential applications in inflammatory and autoimmune disease control.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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