Nasal expression of bitter taste receptors TAS2R in asthma: associations with the disease control, inflammation and bronchial obstruction

Introduction. Bitter taste receptors (TAS2Rs) can be expressed in airway epithelium and are of interest as therapeutic targets for asthma treatment. In a pilot study, we previously identified the most highly expressed TAS2Rs in the nasal epithelium of asthma patients and healthy individuals using NGS. Aim. To determine the relationship between TAS2Rs expression in the nasal epithelium and the disease control, inflammatory markers, airway patency and remodeling in patients with asthma. Materials and methods. The study included 173 patients with asthma (mean age: 46.0 ± 1.13 years; 60% females) of varying severity (56.4% – mild, 41.3% – moderate, 2.3% – severe asthma), predominantly with an uncontrolled disease course (71%). The patients underwent spirometric examination with obstruction reversibility testing and computed tomography (CT) based morphometric analysis of B1 and B10 segmental bronchi following bronchodilator administration. Serum concentrations of total IgE and cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IFN-γ, TNF-α, IL-17A, IL-17F, and IL-22) were measured by ELISA and microparticle-based immunofluorescence assay (LEGENDplex), respectively. Expression of TAS2R4, TAS2R5, TAS2R14, TAS2R20, TAS2R31 and TAS2R38 genes was determined at mRNA level by quantitative reverse transcription PCR (qRT-PCR) in samples obtained from inferior turbinate brush biopsies. Results. Expression of all genes except TAS2R4 showed significant correlations. Decreased asthma control, as assessed by the ACT questionnaire, was associated with increased expression of TAS2R20 ( β = -0.20, p = 0.03) and TAS2R38 ( β = -0.20, p = 0.02) after adjustment for gender, age, body mass index, smoking index, FEV 1 , and IgE level using multiple linear regression. No correlations were found between TAS2R gene expression and lung function parameters or bronchodilator response. Using PLS-SEM analysis, it was found that Th17-driven inflammation, primarily determined by IL-17A levels, is the main factor associated with both CT signs of bronchial remodeling (an inverse association with bronchial size ( β = -0.57, p < 0.001) and a direct association with bronchial wall thickening ( β = 0.34, p = 0.05)) as well as with increased TAS2R expression (most significantly with TAS2R5 ( β = 0.40, p = 0.01) and TAS2R20 ( β = 0.41, p = 0.01)). Bronchial remodeling itself was also associated with upregulation of TAS2R s, particularly TAS2R5 (R 2 = 0.17, p = 0.002) and TAS2R20 (R 2 = 0.15, p = 0.006). However, a significant association with expression level was observed only for the latent variable reflecting bronchial size ( β = -0.33, p < 0.001 for both TAS2R5 and TAS2R20 ). Conclusion. We found evidence of increased TAS2R genes expression with worsening asthma control, as well as in patients with more pronounced bronchial remodeling and elevated serum IL-17A. Given that TAS2R upregulation appears to be a secondary, compensatory response, TAS2R5 and TAS2R20 receptors emerge as the most promising targets for further investigation.