Asthma is a chronic inflammatory disease of the airways that is seen increasingly in westernalized countries. Airway dendritic cells (DC) and epithelial cells play a crucial role in the process of allergic sensitization to house dust mite (HDM), leading to asthma. The nature of this crosstalk is complex but involves endogenous danger signals like uric acid or ATP, which are released upon stress or cell death and act as adjuvants to promote Th2 immunity to the allergen house dust mite (HDM). However, whether HMGB1, another endogenous danger signal involved in several inflammatory diseases, has a role in asthma is unknown. To study this, our lab has generated a new mouse line allowing the specific overexpression of HMGB1 in DCs or in epithelial cells. The objective of this project is to elucidate whether HMGB1 production by these cell types would influence the immune response to HDM and modify the severity of HDM-induced asthma. We will examine how HMGB1 overexpression affects DC and epithelial cell biological functions. Defining in more detail how such functions are modified by HMGB1 might allow us to understand the influence of environmental and genetic risk factors on allergy. The ultimate goal is to halt harmful immune responses to allergens.