Defining the effects of IL33 axis genetic variants on viral induced inflammation in asthma

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to susceptibility and exacerbation. Rhinovirus is a major cause of exacerbations; however the contribution of host genetics and molecular mechanisms underlying these processes and are not well defined. Rhinovirus induces interleukin 33 (IL33) release from bronchial epithelial cells which activates a range of inflammatory cells that drive the exacerbation. As genetic variation in the IL33 and IL33 receptor (IL1RL1) loci have been associated with exacerbation risk we hypothesise that these variants can modulate bronchial epithelial cell responses to virus and how inflammatory cells respond to IL33 ultimately determining the magnitude of inflammation observed. This project will use a combination of cell and molecular biology, immunology and genetics to investigate epithelial cell - inflammatory cell cross talk and has scope to advance our understanding of virus induced exacerbation in asthma where there is an unmet clinical need.