Defining the importance of IL-25 in rhinovirus-induced asthma exacerbations

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Asthma is the most common respiratory disease and has increased over recent decades, such that in many European countries ~30% of children now report wheeze in the last year. Rhinovirus (RV) infection is the dominant individual cause of acute exacerbations in both adults and children. Despite the enormous associated illness current therapies are ineffective and the mechanisms of RV induced asthma exacerbations are poorly understood. Asthmatics produce a molecule in their lungs, IL-25, that is potentially important in causing exacerbations. We aim to understand the role of IL-25 in immune responses to RV infections and asthma exacerbations and determine if this molecule is a suitable candidate for development of better treatments. To determine if IL-25 is associated with immune responses that regulate exacerbation severity we have developed a human experimental RV-induced asthma exacerbation model. Clinical samples from this study will enable us to investigate the association between IL-25 expression and host responses that cause asthma exacerbations. To support human studies we have recently developed the world?s first mouse models of rhinovirus infection and exacerbation of asthma demonstrating numerous asthma related outcomes exacerbated by infection in the mouse. These mouse models of rhinovirus infection and asthma exacerbation will enable investigation within the mammalian airway to establish a causal role in disease for IL-25. The objective of this proposal is therefore to utilize human and models of rhinovirus-induced asthma exacerbation to define a role for IL-25 in the immune response and airways disease, research fundamental to the development of better treatments for asthma exacerbations.