Abstract
Background. The cross-talk between the external and internal environment in the respiratory tract involves macrophage/dendritic cell (DC) transepithelial network. Epithelium triggers dendritic cell-mediated inflammation by producing thymic stromal lymphopoietin (TSLP), IL-33, and IL-17A. The study aimed to evaluate the expression of TSLP, IL-33, and IL-17A in human monocyte derived dendritic cells (moDCs) co-cultured with respiratory epithelium and monocyte derived macrophages (moMφs) in asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. Methods. The study used a triple-cell co-culture model, utilizing nasal epithelial cells, along with moMφs and moDCs. Cells were cultured in mono-, di-, and triple-co-cultures for 24 h. Results. Co-culture with epithelium and moMφs significantly increased TSLP in asthma and did not change IL-33 and IL-17A mRNA expression in moDCs. moDCs from asthmatics were characterized by the highest TSLP mRNA expression and the richest population of TSLPR, ST2, and IL17RA expressed cells. A high number of positive correlations between the assessed cytokines and CHI3L1, IL-12p40, IL-1β, IL-6, IL-8, TNF in moDCs was observed in asthma and COPD. Conclusion. TSLP, IL-33, and IL-17A expression in moDCs are differently regulated by epithelium in asthma, COPD, and healthy subjects. These complex cell–cell interactions may impact airway inflammation and be an important factor in the pathobiology of asthma and COPD.
Highlights
Dendritic cells (DCs) are abundantly represented at the mucosal surfaces which are an interface between the external and internal environment
We found that IL-17A mRNA expression was not decreased in the asthma group compared to controls in monocyte derived dendritic cells (moDCs) co-cultivated with epithelium (p = 0.285), but revealed a significantly lower IL-17A
♦ Kruskal–Wallis test, *#ˆ p < 0.05 Mann–Whitney U test: * asthma vs. controls, # chronic obstructive pulmonary disease (COPD) vs. controls, ˆ asthma vs. COPD. This is the first study that evaluated the impact of interactions between moDCs and epithelial cells co-cultured with moMφs on thymic stromal lymphopoietin (TSLP), IL-33, and IL-17A expression in asthma and COPD
Summary
Dendritic cells (DCs) are abundantly represented at the mucosal surfaces which are an interface between the external and internal environment. Having constant contact with antigens, DCs are thought to be one of the key regulators of the immune response initiation and modulation of inflammation in asthma and chronic obstructive pulmonary disease (COPD) [1,2]. As a result of allergen inhalation airway epithelial cells attract and activate DCs by producing pro-T helper 2. Epithelium derived cytokines (e.g., thymic stromal lymphopoietin (TSLP), IL-33, and IL-25) contribute to the immune response through creation of a positive feedback loop between airway epithelium and inflammatory cells [6,7]. The study aimed to evaluate the expression of TSLP, IL-33, and IL-17A in human monocyte derived dendritic cells (moDCs) co-cultured with respiratory epithelium and monocyte derived macrophages (moMφs) in asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. Co-culture with epithelium and moMφs significantly increased TSLP in asthma and did not change IL-33 and IL-17A mRNA expression in moDCs. moDCs from asthmatics were characterized by the highest
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