Airway regulatory T cells are decreased in COPD with a rapid decline in lung function
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RESEARCH
Airway regulatory T cells are decreased in COPD with a rapid decline in lung function Jonas Eriksson Ström1* , Jamshid Pourazar1, Robert Linder1, Anders Blomberg1, Anne Lindberg1, Anders Bucht1,2 and Annelie F. Behndig1
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: Chronic obstructive pulmonary disease, Disease mechanisms, Lung function decline, Smoking habits, Bronchoalveolar lavage, Regulatory T cells Background Despite many efforts to understand the pathophysiology of COPD, it is still unknown why some long-term smokers develop COPD and some do not. One proposed explanation is differences in the ability to regulate the *Correspondence: [email protected] 1 Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, 90187 Umeå, Sweden Full list of author information is available at the end of the article
immunological response to inhalation of tobacco smoke [1]. Upregulation of regulatory immune cells would restrain airway inflammation and, thus, the development of COPD; while the absence of such upregulation would over time lead to chronic inflammation and eventually COPD. In COPD, airway inflammation is characterized by increased numbers of neutrophils and macrophages [2]. Macrophages are thought to play a major r
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