Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma

Abstract

Background: Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Objectives and Methods: To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. Results: IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. Conclusions: The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity.

Benralizumab strongly reduces blood basophils in severe eosinophilic asthma

“…Increased numbers of basophils are found in the airways of patients after allergen challenge 2 and in patients with fatal asthma 3 . Basophils overexpress receptors for several pro‐inflammatory cytokines in severe asthma 4 and promote type 2 cytokine responses, 1 for example by releasing interleukin‐4 5 . Therefore, basophils might contribute to the severity of asthma.…”

Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights

“…Asthma is characterized by chronic airway inflammation, and hyperresponsiveness (AHR) accompanied by mucus hypersecretion [1]. Triggers of allergic asthma include allergens, fungus (such as Aspergillus fumigatus [2]), viruses (mainly human rhinoviruses (HRV) [3]), and pollutants (including polycyclic aromatic hydrocarbons [4]) [5]. They interact with the airway epithelial cells to initiate the inflammatory response across the airways by releasing of cytokines, particularly IL-25, IL-33, and TSLP [5].…”

“…Triggers of allergic asthma include allergens, fungus (such as Aspergillus fumigatus [2]), viruses (mainly human rhinoviruses (HRV) [3]), and pollutants (including polycyclic aromatic hydrocarbons [4]) [5]. They interact with the airway epithelial cells to initiate the inflammatory response across the airways by releasing of cytokines, particularly IL-25, IL-33, and TSLP [5]. Synergistically with IL-1 and TNF, TSLP stimulates the production of high levels of Th2 cytokines by human MCs [6].…”

Basophil activation: theoretical aspects and use in the diagnosis of allergic diseases

“…Базофильные гранулоциты экспрессируют более 40 различных рецепторов, включая рецепторы к хемокинам (CCR1, CCR2, CCR3, CCR5, CXCR2, CXCR4), цитокинам (IL-3R, IL-25R, IL-33R, IL-18R, VEGFR), компонентам комплемента (CD55, CD86), иммуноглобулинам Е (FcεRI, FcεRII), G (FcγRIII) и D (рецептор пока полностью не охарактеризован, рецепторный комплекс включает galectin-9 и CD44) и др., что позволяет этим клеткам участвовать в развитии как IgE, так и не IgE-опосредованного аллергического воспаления [16,20,70,73,74,76]. В первую очередь, базофилы участвуют в IgE-зависимых реакциях, потому что подобно тучным клеткам, находящимся в тканях, базофилы периферической крови экспрессируют высокоаффинные рецепторы к IgE (FcεRI).…”