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

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

doi:10.1186/s12931-020-01593-9

Jonas Eriksson Ström, Anders Bucht + Show 5 more

Open Access

https://doi.org/10.1186/s12931-020-01593-9

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Abstract

BackgroundDifferences 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.MethodsBronchoscopy 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.ResultsThe 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.ConclusionsCOPD 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

Highlights

Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not
In part 3, the proportion of Forkhead Box P3 (FoxP3)+ regulatory T cells (FoxP3+/CD3+ CD4+ CD25bright) was significantly decreased in COPD rapid compared to COPD non-rapid (Fig. 2)
The multivariable mixed effects regression model showed a statistically significant relationship between decreased proportions of FoxP3+ regulatory T cells and having a rapid decline in lung function (LF) (COPD rapid vs COPD nonrapid; OR 0.38 (0.19–0.77); p = 0.010)

Summary

Introduction

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 the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. Eriksson Ström et al Respir Res (2020) 21:330 the extracellular matrix in the lungs, as well as secrete chemokines that attract other immune cells such as monocytes and lymphocytes. In the latter population, the balance in COPD airways is tipped towards cytotoxic cell types such as CD8+ T cells [3] and NK cells [4]. Tregs have been found to be associated with pack-years rather than COPD status [6] and even to be increased in COPD [7]

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