Impact of smoking on dendritic cell phenotypes in the airway lumen of patients with COPD

Abstract

BackgroundMyeloid dendritic cells (DCs) are increased in the airway wall of patients with chronic obstructive pulmonary disease (COPD), and postulated to play a crucial role in COPD. However, DC phenotypes in COPD are poorly understood.MethodsFunction-associated surface molecules on bronchoalveolar lavage fluid (BALF) DCs were analyzed using flow cytometry in current smokers with COPD, in former smokers with COPD and in never-smoking controls.ResultsMyeloid DCs of current smokers with COPD displayed a significantly increased expression of receptors for antigen recognition such as BDCA-1 or Langerin, as compared with never-smoking controls. In contrast, former smokers with COPD displayed a significantly decreased expression of these receptors, as compared with never-smoking controls. A significantly reduced expression of the maturation marker CD83 on myeloid DCs was found in current smokers with COPD, but not in former smokers with COPD. The chemokine receptor CCR5 on myeloid DCs, which is also important for the uptake and procession of microbial antigens, was strongly reduced in all patients with COPD, independently of the smoking status.ConclusionCOPD is characterized by a strongly reduced CCR5 expression on myeloid DCs in the airway lumen, which might hamper DC interactions with microbial antigens. Further studies are needed to better understand the role of CCR5 in the pathophysiology and microbiology of COPD.

Increased IgA production by B-cells in COPDvialung epithelial interleukin-6 and TACI pathways

“…Second, IgA responses were studied in vitro in co-cultures of AECs and B-cells, while other players (e.g. dendritic cells) could be involved [14,15]. Third, the presence of lymphoid follicles in the COPD lung [33] could also, in turn, modify B-cell/immunoglobulin responses to smoke exposure.…”

“…These follicles consist of a specific arrangement of B-cells, T-cells, dendritic cells and follicular dendritic cells [11,12]. It has been suggested that dendritic cells, numbers of which are increased in COPD small airways, play an important role in the formation of peribronchial lymphoid follicles in this disease [13][14][15]. B-cells are also key players in adaptive immunity, acting not only as immunoglobulin-producing but also as antigen-presenting cells.…”

Long time enzyme replacement therapy stabilizes obstructive lung disease and alters peripheral immune cell subsets in Fabry patients

“…ERT had no significant influence in Fabry patients on mDC or pDC percentage as compared with untreated patients indicating a direct incluence of the disease and or Gb 3 on this cell‐type . The importance of mDC‐s in other obstructive lung diseases is underlined by significantly decreased number of mDC‐s in the small airways and alveoli of COPD patients . As mentioned above, mDC‐s are presented mainly in inflammatory conditions, suggesting these cells may play important role in the development and maintenance of inflammation.…”

Dendritic Cells in Human Lung Disease

“…The small airways in COPD contain cDC with heightened expression of chemokine ligand 20 (CCL20), a potential cause of CD8 T-cell activation 43 . In contrast, there is evidence that some aspects of cDC function may be down regulated in COPD with cDC immaturity associated with airway vascularity and expression of angiogenic factors 44 , and reduced expression of the chemokine receptor CCR5 45 . Furthermore, a recent report indicates that CD1c+ DCs from patients with COPD hinder T-cell effector functions and favor the generation of suppressive T cells.…”