Distinct miRNA expression patterns in circulating eosinophil subtypes and their subtype-derived exosomes in allergic asthma.

IF 6.2 3区 医学 Q2 CELL BIOLOGY
Egle Vasyle, Andrius Januskevicius, Airidas Rimkunas, Jolita Palacionyte, Skaidrius Miliauskas, Kestutis Malakauskas
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引用次数: 0

Abstract

Background: Lung-resident (rEos) and inflammatory (iEos) eosinophil subtypes were initially characterized in mouse models of asthma and have been proposed to contribute differentially to inflammation and remodeling in human allergic asthma (AA). While microRNAs (miRNAs) and their transfer through exosomes may play important regulatory roles in immune signaling in asthma, miRNA profiles specific to eosinophil subtypes remain uncharacterized. This study aimed to identify distinct miRNA expression patterns in circulating eosinophil subtypes and subtype-derived exosomes from AA patients.

Methods: Peripheral blood iEos and rEos were isolated from 22 AA patients and 21 healthy subjects (HS). Next-generation sequencing (NGS) was used to identify differentially expressed miRNAs, and 16 candidates were subsequently selected for validation by quantitative polymerase chain reaction (qPCR) in eosinophil subtypes and in subtype-derived exosomes.

Results: NGS revealed 62 differentially expressed miRNAs in AA iEos and 35 in AA rEos compared with corresponding HS eosinophil subtypes. qPCR confirmed differential expression for 14 of 16 selected miRNAs in eosinophils or their exosomes between AA and HS. miRNA expressions distinguished AA from HS; furthermore, iEos and rEos showed distinct miRNA patterns within the AA group. Notably, AA rEos-derived exosomes showed greater miRNA enrichment than iEos-derived exosomes, implying active exosomal communication. Finally, validated miRNA patterns suggest a predominance of regulatory functions in rEos, whereas iEos displayed a profile consistent with pro-inflammatory activation.

Conclusions: This study provides molecular evidence that eosinophil subtypes are functionally specialized in AA. The differential miRNA patterns of rEos and iEos highlight their complementary regulatory and pro-inflammatory roles and suggest that eosinophil-derived miRNAs merit further investigation as potential biomarkers or modulators of airway inflammation.

过敏性哮喘循环嗜酸性粒细胞亚型及其亚型衍生外泌体中不同的miRNA表达模式
背景:肺常驻(rEos)和炎症性(iEos)嗜酸性粒细胞亚型最初在哮喘小鼠模型中被表征,并被认为对人类过敏性哮喘(AA)的炎症和重塑有不同的贡献。虽然microrna (miRNA)及其通过外泌体的转移可能在哮喘的免疫信号传导中发挥重要的调节作用,但嗜酸性粒细胞亚型特异性miRNA谱仍未表征。本研究旨在鉴定AA患者循环嗜酸性粒细胞亚型和亚型衍生外泌体中不同的miRNA表达模式。方法:对22例AA患者和21例健康人的外周血进行iEos和rEos分离。下一代测序(NGS)用于鉴定差异表达的mirna,随后选择16个候选mirna,通过嗜酸性粒细胞亚型和亚型衍生外泌体的定量聚合酶链反应(qPCR)进行验证。结果:与相应的HS嗜酸性粒细胞亚型相比,NGS在AA iEos和AA rEos中分别发现了62个和35个差异表达的mirna。qPCR证实了嗜酸性粒细胞或其外泌体中16个选定mirna中的14个在AA和HS之间的差异表达。miRNA表达可区分AA和HS;此外,AA组的iEos和rEos表现出不同的miRNA模式。值得注意的是,AA reos衍生的外泌体比ieos衍生的外泌体显示出更高的miRNA富集,这意味着外泌体通信活跃。最后,经过验证的miRNA模式表明rEos的调节功能占主导地位,而iEos显示出与促炎激活一致的特征。结论:本研究提供了嗜酸性粒细胞亚型在AA中功能特化的分子证据。rEos和iEos的差异miRNA模式突出了它们互补的调节和促炎作用,并表明嗜酸性粒细胞衍生的miRNA作为气道炎症的潜在生物标志物或调节剂值得进一步研究。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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