Expression of human Interferon Regulatory Factor 3 (IRF-3) in alveolar macrophages relates to clinical and functional traits in COPD.

IF 5.8 2区 医学 Q1 Medicine
Simonetta Baraldo, Matteo Bonato, Sebastiano Cassia, Paolo Casolari, Laura De Ferrari, Mariaenrica Tiné, Federico Baraldi, Tommaso Bigoni, Anna Maria Riccio, Fulvio Braido, Marina Saetta, Alberto Papi, Marco Contoli
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Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.

Aim: To evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed.

Methods: Lung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry.

Results: A significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001).

Conclusions: Smoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease.

肺泡巨噬细胞中人类干扰素调节因子 3 (IRF-3) 的表达与慢性阻塞性肺病的临床和功能特征有关。
简介慢性阻塞性肺病(COPD)是一种常见的发病和死亡原因。慢性阻塞性肺病的免疫炎症反应失调和增强已有描述。目的:评估慢性阻塞性肺病患者外周肺中导致 IFN 生成的先天性免疫反应中一些研究较少的关键成分的表达情况,包括:IFN 受体(IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors,IFN-receptors):IFN受体(IFNAR1/IFNAR2)、IRF-3和MDA-5。评估了与临床特征和炎症细胞特征的相关性:方法:从 58 名接受胸腔手术的受试者身上采集肺标本,其中包括 22 名慢性阻塞性肺病患者、21 名肺功能正常的吸烟者(SC)和 15 名非吸烟对照组(nSC)。通过免疫组化方法对外周肺中 IFNAR1、IFNAR2、IRF-3 和 MDA-5、嗜酸性粒细胞和活化 NK 细胞(NKp46+)的表达进行了定量分析:结果:与 nSC 受试者相比,COPD 和 SC 受试者肺泡巨噬细胞中 IRF-3 + 的数量明显增加。然而,在 COPD 患者中,IRF-3 + 肺泡巨噬细胞的水平越低,FEV1 就越低,恶化率就越高。慢性支气管炎(CB)的存在也与低水平的 IRF-3 + 肺泡巨噬细胞有关。与 nSC 患者相比,慢性阻塞性肺疾病患者的 NKp46 + 细胞增加,但嗜酸性粒细胞没有增加(p 结论:慢性阻塞性肺疾病患者的 NKp46 + 细胞增加,但嗜酸性粒细胞没有增加:吸烟与较高水平的先天性免疫反应有关,表现为较高水平的 IRF-3 + 肺泡巨噬细胞和 NKp46 + 细胞。在慢性阻塞性肺病中,恶化率、严重气流阻塞和 CB 与较低水平的 IRF-3 表达有关,这表明先天性免疫反应是该疾病特定临床特征的特征。
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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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