Bitter taste receptors TAS2R as promising targets in personalised therapy of asthma

This review summarises current data on the role of ectopic bitter-taste receptors (TAS2R) in the pathogenesis of asthma within a personalised-therapy framework. TAS2R expressed in airway epithelium, airway smoothmuscle cells and immunocompetent cells participate in key inflammatory pathways and regulate bronchial tone. Receptor activation induces airway smooth-muscle relaxation through signalling cascades that are independent of β2-adrenergic receptors and cAMP, maintaining efficacy when β2-agonist sensitivity is reduced. In the T2-high endotype, TAS2R suppress IL-4, IL-5 and IL-13, thereby attenuating eosinophilic inflammation and mast-cell degranulation. In non-T2 asthma, TAS2R inhibit pro-inflammatory mediators (IL-17, IL-8/CXCL8, TNF-α) and curb neutrophil and macrophage activity. Consequently, TAS2R are viewed as promising pharmacological targets, particularly for difficult-to-control asthma resistant to inhaled glucocorticosteroids. The literature already cites compounds with TAS2R-agonist activity, and the search for novel endogenous agonists is ongoing. The evidence underscores the need for further studies to clarify TAS2R molecular mechanisms, evaluate TAS2R-oriented therapy across asthma endotypes, and assess the clinical efficacy and safety of agents designed to personalise treatment based on the genetic and functional characteristics of these receptors.