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

Respir Res. 2024 Aug 19;25(1):315. doi: 10.1186/s12931-024-02952-6.

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.

Keywords: Airflow limitation; Chronic bronchitis; Exacerbations; Innate immunity.

MeSH terms

  • Aged
  • Female
  • Humans
  • Immunity, Innate
  • Interferon Regulatory Factor-3* / biosynthesis
  • Interferon Regulatory Factor-3* / metabolism
  • Macrophages, Alveolar* / immunology
  • Macrophages, Alveolar* / metabolism
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / immunology
  • Pulmonary Disease, Chronic Obstructive* / metabolism

Substances

  • Interferon Regulatory Factor-3
  • IRF3 protein, human