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

• Published in: Respiratory research Vol. 25; no. 1; pp. 315 - 11
• Main Authors: Baraldo, Simonetta, Bonato, Matteo, Cassia, Sebastiano, Casolari, Paolo, De Ferrari, Laura, Tiné, Mariaenrica, Baraldi, Federico, Bigoni, Tommaso, Riccio, Anna Maria, Braido, Fulvio, Saetta, Marina, Papi, Alberto, Contoli, Marco
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.08.2024; BioMed Central; BMC
• Subjects: Aged; Airflow limitation; Chronic bronchitis; Exacerbations; Female; Health aspects; Humans; Immune response; Immunity, Innate; Immunohistochemistry; Innate immunity; Interferon; Interferon Regulatory Factor-3 - biosynthesis; Interferon Regulatory Factor-3 - metabolism; Lung diseases, Obstructive; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Male; Methods; Middle Aged; Physiological aspects; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - metabolism; Italy; Exacerbations; Innate immunity; Chronic bronchitis; Airflow limitation
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-024-02952-6

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. 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. 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. 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). 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.