Mast cell- epithelial interactions – drivers of chronic airway disease?

Interactions between the epithelium and MCs are likely to be major drivers of the development and progression of chronic airway diseases. The main aim of this research program is to define the interaction between mast cells and the epithelium in the pathobiology of chronic respiratory diseases such as asthma under conditions that are known to damage the airways.
This will be done by investigating:
I) the density and phenotype of intraepithelial MCs in human lung tissue from different chronic airway diseases and how this is related to damages and remodelling of the corresponding epithelium.
II) how MCs home into the epithelial layer by investigating integrin expression on human MC and secretion of MC attracting mediators released from primary epithelial cells in response to damage and respiratory infections.
III) how MC mediators affect in vitro cultured primary epithelial cells from asthma patients, investigating inflammatory responses and barrier function of the epithelium. This system will also be used to investigate the effect of conventional pharmacological treatments.

The proposed translational research programme has unique potential to answer these questions by combining studies of human experimental models and investigations in volunteers and patients with different sub-phenotypes of asthma. The overall purpose of the research programme is to define mechanisms that may be applied to improve and specify diagnosis and treatment of different phenotypes of asthma. The hypothesis is that MC mediators disrupts the barrier function of the airway epithelium and causes an enhanced inflammatory response in patients with chronic airway disease.