Spleen Tyrosine Kinase and Bruton Tyrosine Kinase Signaling in Allergic Asthma: Molecular Mechanisms, Therapeutic Targets, and Future Perspectives

AbstractAsthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness,reversible airflow obstruction, mucus hypersecretion, and airway remodeling. Although inhaledcorticosteroids and biologic therapies have improved asthma management, many patients withsevere asthma continue to experience uncontrolled symptoms and frequent exacerbations. Spleentyrosine kinase (SYK) and Bruton tyrosine kinase (BTK) have emerged as promising therapeutictargets because of their important roles in immunoglobulin E (IgE)-mediated allergicinflammation. This narrative review summarizes the molecular mechanisms of SYK and BTKsignaling in allergic asthma and evaluates their potential as therapeutic targets. Relevantliterature was identified through PubMed, Scopus, Web of Science, and Google Scholar, andexperimental, clinical, and review articles were critically evaluated. Current evidence shows thatSYK initiates FcεRI-mediated signaling after allergen-induced IgE receptor activation, whileBTK enhances downstream signaling through phospholipase Cγ activation, calciummobilization, and inflammatory gene expression. Preclinical studies have demonstrated thatinhibition of these kinases reduces mast cell degranulation, eosinophilic inflammation, cytokineproduction, mucus hypersecretion, and airway hyperresponsiveness. Early clinical studies alsosuggest that SYK and BTK inhibitors may provide effective targeted therapies for severe allergicasthma. Overall, targeting the SYK–BTK signaling pathway represents a promising precisionmedicine strategy for allergic asthma. However, further translational research and well-designedclinical trials are needed to establish their long-term efficacy, safety, and clinical value.