Abstract
BackgroundDendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.MethodsFour-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.ResultsConcentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.ConclusionAn imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users.
Highlights
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterised by both local abnormalites and systemic abnormalities [1]
Using an established method to analyse human bronchoalveolar lavage fluid Dendritic Cell (DC) [10,11,12,13], we have shown that airway myeloid Dendritic Cell (mDC) of asymptomatic smokers show a profound adaptation to cigarette smoke exposure, including a strong upregulation of antigen-recognition receptors such as CD1a, Blood Dendritic Cell Antigen (BDCA)-1 or Langerin and co-stimulatory molecules such as CD86 [11]
We demonstrate a specific increase in the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on blood mDCs and a specific decrease in the anti-inflammatory co-stimulatory molecule PDL1 on blood Plasmacytoid Dendritic Cell (pDC) in chronic obstructive pulmonary disease (COPD)
Summary
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterised by both local abnormalites (including a specific type of airway inflammation) and systemic abnormalities (including typical co-morbidities and various degrees of systemic inflammation) [1]. An abnormal immune response to inhaled noxious agents is a central pathogenetic feature of COPD, leading to lymphoid follicle formation around the airways and small airway obstruction [1]. Less than 30% of all smokers develop COPD [2] and it is still unclear which specific immunologic features account for COPD development. Dendritic cells (DCs), which can be subdivided into myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), control pulmonary immune responses. Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The expression of function-associated surface molecules on circulating DCs in COPD is unknown
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