Keratinocyte/dendritic cell interactions in the skin determines allergic sensitization and the severity of asthma to house dust mite allergen 

Asthma is a chronic inflammatory disease of the airways that is seen increasingly in westernalized countries. Studies have shown that a majority of patients with asthma have suffered from atopic dermatitis (AD) in their childhood. Moreover, patients with AD develop more severe steroid-resistant forms of asthma. The mechanisms involved in the progression from AD to asthma are currently unknown. Several reports argue that this might mainly due to an aberrant cytokine production by keratinocytes. However, how allergen-induced keratinocyte responses promote the development of asthma is unknown. We propose that sensitization via the skin and asthma development later on might require a crosstalk between keratinocytes and professional antigen presenting cells called dendritic cells (DCs), and that this crosstalk might affect the severity of the disease. In this project, we will test the contribution of DC populations to the process of sensitization using different mouse strains allowing the selective depletion of skin DC populations at the time of allergen exposure. The contribution of keratinocyte will be tested using other strains allowing the overexpression of HMGB1, an endogenous danger signal involved in several inflammatory diseases. Understanding how keratinocytes and DCs communicate in the skin could bring clarity on the process of allergic sensitization and eventually unravel new therapeutic and preventive avenues for asthma