Grant: Project Grant

Our lungs are relentlessly bombarded by foreign particles and must continually work hard to discriminate between dangerous and harmless ones. Considering the volume of allergen-filled air inhaled every day, the prevalence of inflammation and lung diseases is surprisingly low. Nonetheless, the incidence of asthma has increased alarmingly over the last two decades. There are over 235 millions of asthmatics around the world and its prevalence is around 10% in Canada. Asthma has become an important cause of mortality, decreases the quality of life, and its ensuing health care costs continue to increase every year. Recently, a molecule found at the surface of our cells called CD200 was shown to be involved in the control of inflammation. Our preliminary data show that allergen exposure increases CD200 expression on macrophages, cells located in the lung. Interestingly, no increase of CD200 on these cells was observed in allergic asthmatic animals. Since these macrophages are the most numerous immune cells in the respiratory system and their primary role is to stop unnecessary inflammatory responses, our data therefore suggests that increasing CD200 may contribute to reduce lung inflammation. To investigate whether CD200 is important in protecting against asthma pathogenesis, we treated allergic asthmatic animals with a synthetic CD200 prior to allergen challenge. This treatment effectively reduced their asthma symptoms. In view of these results, this proposal aims to confirm our preliminary data and further investigate the mechanisms involved in the protective role of CD200, through the use of both acute and chronic asthma models. We will also determine the relevance of our data by studying CD200 expression on human macrophages with and without allergic asthma, and also, before and during the allergy season. A better understanding of CD200 protecting functions may highlight new targets for asthma therapy, leading to improved control of this lifelong disease.