Role of CD97/ADGRE5 in allergic asthma

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The central aim of our proposal is to elucidate the role of CD97/ADGRE5 in the development and maintenance of asthma, a considerable public health problem with increasing prevalence. Allergic asthma is an inappropriate T helper cell 2 (Th2)-mediated immune response to harmless allergens which is initiated by signals delivered by antigen presenting cells which activate naïve CD4 T-cells via the T-cell receptor and accessory molecules. CD97, an adhesion G protein-coupled receptor (GPCR) strongly present in immune cells, acts with its ligand CD55 as a costimulatory molecule and activator of naïve CD4+ T-cells. It is an important mediator of neutrophilic migration and host immune defense and is linked to rheumatoid arthritis and multiple sclerosis, but there is no information on the involvement of CD97 in asthma so far. Thus, we will characterize the role of CD97 in asthma pathophysiology in various models of allergic asthma using Cd97-deficient (Cd97-/-) and Cd97-/- chimeric mice. Our own initial data have revealed an obvious worsening of acute asthma after loss of CD97. We will further investigate the impact of the application of an established CD97 antibody, which enriches in the lung, on murine asthma development. To elucidate the underlying mechanisms leading to the asthma-modulating effects in Cd97-/- and CD97 antibody-treated mice, we will apply cell culture and in-vivo adoptive cell transfer methods. Finally, we will evaluate the role of the ligand CD55 and its interaction with CD97 in asthma development using Cd55-/- and Cd55-/-/Cd97-/- chimeric mice. The results of our project will not only provide new insights in the function of CD97 in asthma pathophysiology but may also lead to novel strategies for interventions to face allergic immune diseases.