Airway regulatory T cells are decreased in COPD with a rapid decline in lung function

Jonas Eriksson Ström, Jamshid Pourazar, Robert Linder, Anders Blomberg, Anne Lindberg, Anders Bucht, Annelie F Behndig, Jonas Eriksson Ström, Jamshid Pourazar, Robert Linder, Anders Blomberg, Anne Lindberg, Anders Bucht, Annelie F Behndig

Abstract

Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that-among COPD patients-the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1.

Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

Results: The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function.

Conclusions: COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1. Trial registration Clinicaltrials.gov identifier NCT02729220.

Keywords: Bronchoalveolar lavage; Chronic obstructive pulmonary disease; Disease mechanisms; Lung function decline; Regulatory T cells; Smoking habits.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Part 3: Flow cytometry of BAL fluid from COPD subjects. a Activated T helper cells in (in percentage of T helper cells). b FoxP3+ regulatory T cells (in percentage of activated T helper cells). Data shown as median and IQR. NS not significant, LF lung function. Shown p-value calculated using the Mann–Whitney U-test. See Additional file 1 for corresponding data in tables
Fig. 3
Fig. 3
Relationship between FoxP3+ regulatory T cells (in percentage of activated T helper cells) and annual decline in FEV1 (ml/year). Shown r- and p-values determined by Spearman’s rank correlation coefficients

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Source: PubMed

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