Epithelial/immune interactions underlying development and resolution of allergic airway inflammation and remodelling influence of genes and environment.

The lung is held in homeostasis by a complex network of immune cells interacting with the pulmonary epithelium. In asthmatic subjects there is a failure in the functional integrity of one or more of these components leading to a breakdown in tolerance to airborne environmental allergens. Gene environment interactions are critical in the initiation of this process. We hypothesise that epithelial interactions with the immune system are influenced by genetic and environmental factors and are vital in determining whether allergen inhalation results in tolerance or chronic allergic inflammation and remodelling. We will use mouse models to determine how inhaled allergen affects lung homeostatic networks to delineate the mechanisms which determine whether allergen exposure leads to acute resolving inflammation or chronic inflammation and remodelling. We will investigate the cells and molecules involved in the generation and resolution of house dust mite induced allergic inflammation and how these parameters are affected by age of the mouse, viral infection or inhaled pollutants. We will determine the functional role of key asthma susceptibility genes in the development of allergic inflammation and remodelling. We will use complex mutant mice to dissect the regulatory and pro-fibrotic functions of epithelial TGFbeta signalling pathways after HDM exposure.