Decreased FOXP3 expression in small airways of smokers with COPD

Abstract

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.

From the authors:

“…At the same time, these changes could be the first step towards tumour genesis, as it is now known that Treg cells decrease cellular immune anti-tumour defence [3]. Opposite changes in peripheral airways in COPD patients which we reported in our article, possibly enhance the autoimmune process [1]. Therefore, the events occurring in central and peripheral airways should be regarded as independent local reactions of the immune system.…”

T-regulatory cells in COPD or tumour environment

“…We also found an increased proportion of these cells in BALF from lung cancer patients: the mean proportion of CD4+/CD25+ in the CD4+ population was 47% in cancer patients and was higher than that in patients with interstitial lung disease (14%) [7]. Therefore, the results of ISAJEVIS et al [1] who found that FOX3 positive cells are upregulated in large airways and downregulated in the small airways could be affected by tumour stage and location.…”

“…We read with great interest the paper by ISAJEVS et al [1] published recently in the European Respiratory Journal. The role of regulatory cells in the pathomechanism of chronic obstructive pulmonary disease (COPD) is an interesting issue and has been the subject of our studies on the systemic effects in COPD.…”

Evasion of COPD in smokers: at what price?

“…In other studies, the lungs of smokers with COPD and emphysema have been found to have fewer Tregs and less FoxP3 mRNA than the lungs of healthy smokers, who had more Tregs than the nonsmokers [19,20]. Furthermore, smokers with COPD were found to have an upregulation of FoxP3+ T-cells in the large airways, but had a downregulation of FoxP3+ T-cells in the small airways, the main site of pathological involvement in COPD, which correlated with airflow limitation [21]. This suggests that in smokers with normal lung function or mild COPD, Tregs, by controlling the immune reaction, might prevent the development of severe disease.…”