Coughing up dendritic cells: The impact of asthma on dendritic cell development at the cellular and the molecular level

Development of allergic asthma requires dendritic cells (DC). Novel therapies could involve interference with the development and relative abundance of functionally specialized lung DC subsets. DC differentiate from multipotent progenitors via subset-specific precursors. Inflammation can alter the contribution and differentiation choices of progenitors/precursors. Accordingly, asthma drastically changes airway DC subset distribution and preliminary experiments show alterations in bone marrow progenitors, suggesting effects on DC development. However, knowledge on the DC progenitors/precursors generating distinct lung DC subsets remains limited and evidence on how asthma affects this is almost completely elusive. I propose that DC precursor development, selection and differentiation choices are affected by allergen-induced airway inflammation and this affects the outcome of pulmonary immune responses to allergens. To elucidate how asthma affects DC progenitors/precursors at the cellular and the molecular level, I will undertake the following research plans: -Determine the consequences of allergic asthma on the distribution and DC differentiation capacity of murine DC progenitors and precursors -Characterize the cytokines and molecular mechanisms regulating murine lung DC subset development under steady state and asthmatic conditions -Validate the pathways of lung DC development in the human system This will aid identification of DC development pathways amenable to therapeutic intervention.