Participation of TSLP, IL-33 and IL-25 in the interactions between respiratory epithelial cells, dendritic cells and macrophages in obstructive respiratory diseases

Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic respiratory diseases in our society. Their essence is inflammation in the lower respiratory tract, which leads to obstruction (narrowing) of the bronchi. The main symptoms of asthma and COPD are shortness of breath, wheezing heard when breathing, cough (dry or tough), and decreased exercise tolerance. The manifestation of the disease depends both on genetic predisposition as well as on environmental factors, such as allergens that favor the development of asthma and tobacco smoke, which is the most important cause of COPD. Both asthma and COPD are very complex and variable diseases. The diagnosis of asthma and COPD can be difficult because these diseases sometimes have quite similar symptoms. In practice, asthma and COPD are often two sets of respiratory diseases whose pathophysiology, clinical symptoms and treatment overlap to a large extent. One of the most important phenomena in the development and course of these diseases is the influx of various inflammatory cells into the respiratory tract. The presence and activity of specific groups of cells in the respiratory tract is closely related to the development of the symptoms of the disease. Typical cells for asthma are eosinophils, and in COPD the dominant role is played by neutrophils (neutrophils).However, this classic picture of airway inflammation ascribed to asthma or COPD is often difficult to observe as there are many mixed and overlapping phenotypes. The constant presence of an increased number of eosinophils and neutrophils in the lungs leads to the breakdown of these cells and the release of harmful messengers causing damage to the airways, leading to symptoms of the disease. As a result, the production of a large amount of secretions and irritation of the nerve endings are observed. For the patient, this means coughing, shortness of breath, worse respiratory test results and the need for frequent visits to the doctor due to respiratory infections. The cells in the airways are able to communicate thanks to the huge number of transmitters they produce. The cytokines produced by the epithelium: TSLP, IL-33 and IL-25 are important proteins that shape the allergic response of the organism. Thanks to these cytokines, it is possible to "talk" between the groups of cells that directly create inflammation in the airways. The role of TSLP, IL-33 and IL-25 is widely studied in asthma as a disease that is often allergic. The role and function of these cytokines in COPD are unknown. Atopy, i.e. a genetically determined complex of disorders of the immune system resulting from the body's reaction to a given allergen, is associated with TSLP, IL-33 and IL-25. In the light of recent scientific publications that emphasize the individualization of the diagnosis and treatment of obstructive respiratory diseases, it is important to understand the underlying biological reactions of allergic inflammation, which may occur in both asthma and COPD, especially in COPD with an allergic phenotype (eosinophilic inflammation in COPD). The presented project aims to assess the interactions and relationships between the types of cells forming the immune response of the respiratory system: macrophages, respiratory epithelium and dendritic cells through TSLP, IL-33 and IL-25 expression in atopic and non-atopic obstructive respiratory diseases. The project is to be carried out in a complex (three-layer) and advanced in vitro model that reflects the site of an active immune response in the human airways. The material for the study will be the respiratory epithelium isolated from nasal brush swabs, as well as macrophages and dendritic cells isolated from peripheral blood cells from patients with COPD, asthma and healthy people. Careful analysis of the biochemical reactions underlying allergic inflammation in patients with asthma and COPD will increase knowledge in the field of immunology and provide a better understanding of the mechanisms that govern the course of obstructive respiratory diseases.