Airway Inflammation and remodelling

Professor Clare Lloyd, Head of Group

Airway remodelling (click for large version)

We have developed a murine model of allergen induced airway inflammation and remodelling, and used this model to identify key interactions leading to the development of pathology. The model recapitulates many of the features characteristic of the human disease, including eosinophilic inflammation, airway hyperresponsiveness, mucus production, extracellular matrix deposition, airway smooth muscle cell proliferation, and TGFβ secretion. Importantly, the changes to airway structure were sustained in the absence of further allergen challenge. We have defined roles for Th2 cells and eosinophils in the development of airway remodelling. Moreover we have determined that Th2 cytokines such as IL-13 and IL-4, and the profibrotic growth factor TGF-β play an important part in remodelling after chronic allergen challenge.

The Lloyd lab is investigating the epithelial-immune interactions underlying development and resolution of allergic airway inflammation, and we are particularly focused on how genetic background of the individual and the external environment influence these interactions. We have developed models to examine the role that environmental factors such as age, infection history and pollution have on the development of allergic responses.

Carla and microscope In addition we are investigating the contribution of resident lung cells to airway remodelling. We will investigate the ontogeny of fibroblasts during the development of airway remodelling in vivo. In particular, we are determining molecules responsible for mobilisation and trafficking of fibroblasts within the allergic lung following allergen challenge, in mouse and human models. We aim to investigate the contribution of the epithelial mesenchymal trophic unit (EMTU) to the development of airway remodelling by determining whether allergen induced airway remodelling and inflammation are parallel or sequential events. We are developing novel models to test the hypothesis that interaction of inhaled allergen and epithelium with defective repair mechanisms activates the EMTU and leads to airway remodelling.