Immune-regulatory microRNA expression levels within circulating extracellular vesicles correspond with the appearance of local symptoms after seasonal flu vaccination

Immune-regulatory microRNA expression levels within circulating extracellular vesicles correspond with the appearance of local symptoms after seasonal flu vaccination
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DOI:
10.1371/journal.pone.0219510
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发表时间:
2019-07-09
期刊:
影响因子:
3.7
通讯作者:
Oshiumi, Hiroyuki
Oshiumi, Hiroyuki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miyashita, Yusuke;Ishikawa, Kana;Oshiumi, Hiroyuki

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细胞外囊泡(EV)含有调节先天性免疫应答(如促炎细胞因子的产生)的微小RNA(miRNA)。疫苗接种后促炎细胞因子的过度产生可引起局部不良反应,如疼痛、瘙痒、肿胀和发红。先前的研究表明,循环EV miR-451 a调节先天免疫应答,并且血清EV中的miR-451 a水平与响应于流感疫苗的促炎细胞因子表达水平呈负相关。由于过度的促炎细胞因子产生是疫苗接种局部不良反应的原因,我们研究了血清EV中的miR-451 a水平是否与疫苗接种部位的局部症状相关,如疼痛、瘙痒、肿胀和发红。有趣的是,血清EV中的miR-451 a水平与疫苗接种后的症状数量呈负相关。我们测定了血清EV中其他几种免疫调节miRNA的水平。使用miR-22,miR-29 a,miR-451 a和miR-107的免疫调节miRNA水平,我们计算了每个健康供体的标准化miRNA水平,发现标准化miRNA水平与疫苗接种后局部症状的数量显著相关。我们的数据表明,血清EV中的免疫调节miRNA水平可用作评估流感疫苗接种后局部症状的生物标志物。
Extracellular vesicles (EVs) contain microRNAs (miRNAs) that regulate the innate immune responses, such as the production of pro-inflammatory cytokines. The excessive production of pro-inflammatory cytokines after vaccination can cause local adverse reactions, such as pain, itching, swelling, and redness. Previous studies have shown that circulating EV miR-451a regulates innate immune responses, and miR-451a levels in serum EVs are negatively correlated with the pro-inflammatory cytokine expression levels in response to the influenza vaccine. Since excessive pro-inflammatory cytokine production is a cause of the local adverse reactions to vaccination, we investigated whether miR-451a levels in serum EVs correlate with local symptoms at the vaccination site, such as pain, itching, swelling, and redness. Interestingly, miR-451a levels in serum EVs were inversely correlated with the number of symptoms after vaccination. We determined the level of several other immuneregulatory miRNAs in serum EVs. Using the immune-regulatory miRNA levels of miR-22, miR-29a, miR-451a, and miR-107, we calculated a normalized miRNA level for each healthy donor and found that the normalized miRNA levels were significantly correlated with the number of local symptoms after vaccination. Our data indicated that immune-regulatory miRNA levels in serum EVs can be used as biomarkers to assess local symptoms after influenza vaccination.