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

The 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-kappa B, 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

Automated summary

The house dust mite is a major source of airborne allergens worldwide, and exposure to these allergens can lead to the development of asthma. Mite-derived allergens activate various lung cell types and induce chronic inflammation. This article focuses on the role of CRAC channels in the recognition and signaling pathways of mite-derived allergens, and discusses the potential of targeting CRAC channels as a therapy for mite-induced asthma.