Epithelial cell derived Thymic Stromal Lymphopoietin (TSLP) instructs dendritic cells (DCs) via the expression of OX40L to induce Th2 polarization and is both necessary and sufficient for the development of airway inflammation. TSLP and OX40L are therefore promising targets for the development of new therapies for allergic asthma. The aim of this project is to study the potential of targeting human TSLP and human OX40L for intervening with the initiation and/or progression of allergic asthma in vivo, using a humanized mouse for asthma model. The proposed model is unique since it enables to particularly evaluate the effect of potential therapeutic compounds, in our case (anti-)TSLP and (anti-)OX40L, on human haematopoietic cells in an in vivo system. Information acquired in this project should therefore lead to important go-no go decisions to further advance this therapeutic strategy to the clinic. All experimental work will be performed in the laboratory of Prof. Bart Lambrecht (University Hospital, Ghent, Belgium). Prof. Bart Lambrecht is an expert on murine models of asthma and is focused specifically on DC biology. In his laboratory all facilities and expertise are available to perform the proposed experiments. In addition, the group heads have extensive experience in mentoring and guiding post docs. The proposed work will allow me to further develop my recently founded translational research line directed at the immunopathology of allergic asthma in young children. On return to my home institute I will incorporate my research in the Center of Molecular and Cellular Intervention of the University Medical Center Utrecht (head Prof. B. Prakken). The combination of my current expertise in human immunology, my clinical expertise as an MD-pediatrician and the expertise I will gain in the laboratory of Prof. Lambrecht on mouse models of asthma will enable me to take a strong competitive research position and as I hope to contribute to European excellence.
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