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Asthma

Congratulations are in order for Anant Parekh, Professor of Physiology here in the Department, and postdoctoral scientist Yu-Ping Lin, whose paper has recently been accepted by Molecular Cell. 

Their paper, entitled The allergen Der p3 from house dust mite stimulates store-operated Ca2+ channels and mast cell migration through PAR4 receptors,  looks at a radical new approach to combating asthma. 

Asthma is a chronic disease of the airways and is estimated to affect more than 300 million people worldwide. In the clinic, asthma presents with a range of phenotypes indicating it is a heterogeneous disease and it is poorly controlled by current therapies in an increasing cohort of patients.

One strategy is to target risk factors that are associated with the development of asthma. These factors include genetic predisposition and environmental influences such as exposure to inhaled allergens, particularly those derived from the pyroglyphid house dust mite.

The house dust mite is the principal source of perennial allergen in humans and the European Community Respiratory Health Survey I has reported a prevalence for asthma with house dust mite sensitisation as high as 21%; although there was significant geographic variation between member states. The primary allergens in Dermatophagoides Pteronyssinus are the Der p proteins, of which there are more than twenty.

Allergens from house dust mite stimulate multiple cell types in the lung to release chemical signals that help orchestrate the subsequent inflammatory response. Interventions that impair the ability of mite allergens to activate the immune system should therefore be of significant therapeutic benefit. One way to accomplish this would be to reduce indoor exposure to mite allergens. This approach has spawned a lucrative domestic mite-removal industry but a meta-analysis of randomized studies found no beneficial effect of these manoeuvres on asthma.

An alternative strategy is to understand how house dust mite-derived allergens activate immune cells and the airway remodelling process that is characteristic of chronic asthma, as this will better inform focused drug design for more effective treatments. 

This new study from Parekh, Lin, and their colleagues has found that house dust mite activates calcium channels in different cell types that are all involved in the pathogenesis of asthma and opening of the Ca2+ channels stimulates immune cell activity. Although the dust mite contains many allergens, Lin et al. discovered that just one particular allergen, Der p3 was the key molecule that activates the channels. They went on to demonstrate that a combination therapy targeting both the calcium channels and Der p3 suppressed immune cell activation, raising the real possibility of a new treatment for combating asthma. 

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To learn more about the research carried out by Parekh, Lin and their lab group, visit their web page.