Targeting innate immune memory for prevention of asthma

Asthma is one of the most prevalent allergic diseases affecting 10-14% of Canadians. Asthma leads to shortness of breath, coughing, wheezing, and abundant inflammation in the lungs. Inflammation is caused by excessive numbers of immune cells and each of these immune cells can more easily be activated than in healthy individuals. Many immune cells just live for a few days. They then need to be replaced by new immune cells that have just been produced by stem cells. Researchers, including us, have recently discovered that the genes of the stem cells can be locked in with specific configurations. We term this "reprogramming". Reprogrammed stem cells with altered genetic code produce immune cells that are, depending on the configuration, more or less inflammatory. We propose in this project that allergen exposure induces reprogramming in stem cells, which then leads to the production of highly inflammatory immune cells that cause asthma. The overall goal of this project is to dissect in mouse models the stem cell dynamics and reprogramming upon allergen exposure. Better understanding asthma development will ultimately lead us to identify improved medications or vaccines for this devastating disease. Thus, next, we will investigate a natural, medical component (glucan) that is in clinical trials for several diseases. Specifically, we will study whether glucan can reprogram the stem cells in a beneficial way that leads to diminished allergy symptoms. Ultimately, this project will guide us towards a broadly applicable new medication strategy for asthma and potentially other allergic diseases.