Raised interferon-β, type 3 interferon and interferon-stimulated genes - evidence of innate immune activation in neutrophilic asthma
Raised interferon-β, type 3 interferon and interferon-stimulated genes - evidence of innate immune activation in neutrophilic asthma
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DOI：
10.1111/cea.12809
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发表时间：
2017-03-01
影响因子：
6.1
通讯作者：
Louis, R.
中科院分区：
文献类型：
--
作者：
da Silva, J.;Hilzendeger, C.;Louis, R.
背景干扰素在天然免疫中起重要作用。先前的研究报道了特应性哮喘患者支气管上皮细胞和支气管灌洗液细胞中病毒诱导干扰素（IFN）-α、IFN-β和IFN-λ的缺陷。哮喘是一种异质性疾病，包括不同的炎症表型，其中一些可能涉及先天免疫激活，在没有明显感染的情况下。目的本研究的目的是调查是否哮喘的严重程度或特定的细胞痰模式可能与先天免疫激活的证据。IFN-λ 2/3检测57例哮喘患者痰液中白细胞介素28（IL-28 A/B）和干扰素刺激基因（ISGs）如粘液病毒抗性1（Mx 1）、寡腺苷酸合成酶（OAS）和蛇毒蛋白（viperin）的表达结果哮喘患者肺组织中IFN-β、IFN-λ 1/IL-29、IFN-β 1/IL-29、OAS和Viperin在哮喘组和健康对照组中均表达，而IL-28在任何组中均不表达。这种过度表达仅限于嗜酸性粒细胞哮喘患者（痰中性粒细胞>= 76%），而嗜酸性粒细胞哮喘患者（痰嗜酸性粒细胞>= 3%）与健康受试者没有差异，甚至表现出较低的Mx 1表达。根据临床哮喘severity.Conclusion和临床相关性中性粒细胞，但不是嗜酸性粒细胞，哮喘显示IFN-β，IFN-λ 1/IL-29和ISGs在他们的痰细胞，可能反映正在进行的先天免疫激活的过度表达。
Background Interferons play an important role in innate immunity. Previous studies report deficiency in virus induction of interferon (IFN)-alpha, IFN-beta and IFN-lambda in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection.Objective The aim of this study was to investigate whether the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation.Methods Here we investigate the expression of IFN-beta, IFN-lambda 1 (IL-29), IFN-lambda 2/3 (IL-28A/B) and the interferon-stimulated genes (ISGs) such as myxovirus resistance 1 (Mx1), oligoadenylate synthetase (OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects.Results We observed increased expression of IFN-beta, IFN-lambda 1/IL-29, OAS and viperin in asthmatics compared with healthy subjects, while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils >= 76%), while eosinophilic asthmatics (sputum eosinophils >= 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was observed according to clinical asthma severity.Conclusion and Clinical Relevance Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-beta, IFN-lambda 1/IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation.