Therapeutic targeting of lysosome-triggered inflammatory channels in nasal and upper-airway allergic conditions

Nasal and upper airway allergic disorders, such as allergic rhinitis and allergy-associated sinus inflammation, constitute a major global health problem because of their high prevalence and significant negative impact on quality of life. There are indications that lysosomes to a large extent participate in the process of airway inflammation, by both starting and intensifying the immunological signaling via certain ionic channels. The resulting release of pro-inflammatory cytokines occurs through calcium signaling mediated by lysosome activity, and this is particularly the case when the NLRP3 inflammasome is activated. Hence, mucosal inflammation and increased airway sensitivity develop. Recent studies have identified the lysosomal ion channels, such as the two-pore channels (TPCs) and transient receptor potential mucolipin (TRPML), as the main regulators of these processes. The animal models used for preclinical settings confirmed that manipulation of these channels pharmacologically or genetically had a promising anti-inflammatory effect, thus marking them as possible future therapeutic targets. Moreover, such approaches may help reduce systemic side effects and enhance the efficacy of existing treatments. This article reviews the molecular mechanisms, therapeutic strategies, and translational potential of lysosome-triggered inflammatory signaling in nasal and upper airway allergic disorders. Targeting lysosomal signaling pathways may provide new opportunities for precision-based therapies in allergic airway inflammation.