Immune responses underlying COPD pathology

Chronic obstructive pulmonary disease (COPD) describes a largely untreatable and common set of lung pathologies affecting >80 million people, predominantly in low and middle income countries. The WHO estimate that, by 2030, COPD will be the third largest cause of death worldwide. It is known that lung cells called alveolar macrophages play a crucial role in causing and maintaining the symptoms of COPD. However, alveolar macrophages are normally protective against lung infections and inflammation. Our interests lie in what causes alveolar macrophages to change from being protective, to causing severe lung damage.

Our current collaboration (between the Universities of Cape Town and York) has addressed this question using a mouse model of chronic lung inflammation. By using model systems we have been able to more fully characterise the alveolar macrophages during disease, and have used geneticallymanipulated models to examine the specific functions of these cells. In this model we have identified a number of novel genes which are expressed in alveolar macrophages and show association with the onset of irreversible pathology which closely resembles that observed in COPD patients. These genes represent not only an opportunity to better understand how alveolar macrophages orchestrate COPD, but also represent a first wave of future potential therapeutic targets for a disease which currently lacks an effective treatment.

In order to fully utilise and expand our understanding gained in model systems, we aim to establish a network of researchers experienced in both clinical and experimental COPD biology. To initiate this we will initially expand our collaboration to include the University of Southampton, a recognised centre of excellence for clinical research into pulmonary disease. This work will validate the findings we have made in our experimental model and allow the development of a translational research group to study in depth the role of alveolar macrophages in COPD.