House dust mite allergens, store‐operated Ca2+ channels and asthma

Abstract

AbstractThe house dust mite is the principal source of aero‐allergen worldwide. Exposure to mite‐derived allergens is associated with the development of asthma in susceptible individuals, and the majority of asthmatics are allergic to the mite. Mite‐derived allergens are functionally diverse and activate multiple cell types within the lung that result in chronic inflammation. Allergens activate store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels, which are widely expressed in multiple cell types within the lung that are associated with the pathogenesis of asthma. Opening of CRAC channels stimulates Ca2+‐dependent transcription factors, including nuclear factor of activated T cells and nuclear factor‐κB, which drive expression of a plethora of pro‐inflammatory cytokines and chemokines that help to sustain chronic inflammation. Here, I describe drivers of asthma, properties of mite‐derived allergens, how the allergens are recognized by cells, the signalling pathways used by the receptors and how these are transduced into functional effects, with a focus on CRAC channels. In vivo experiments that demonstrate the effectiveness of targeting CRAC channels as a potential new therapy for treating mite‐induced asthma are also discussed, in tandem with other possible approaches. image