Tissue recruitment of type 2 effector cells

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Allergic inflammation of the lung and atopic dermatitis are two prominent examples of type 2 immunity-driven diseases where several different IL-4/IL-13-expressing effector cells of the immune system enter the lung or skin, respectively, and cause pathology. The IL-4/IL-13-induced transcription factor STAT6 is known to play a critical role for recruitment of eosinophils and other effector cells but it is poorly defined, which STAT6-regulated genes in stromal or hematopoietic cells are critical for this process. In this research project we will therefore investigate the STAT6-dependent mechanisms regulating development and tissue recruitment of IL-4/IL-13-expressing effector cells including eosinophils during type 2 immune responses. We will work with a model of Aspergillus fumigatus-induced allergic lung inflammation by intranasal application of live conidia. For type 2 immune responses in the skin we will use an IgE- and basophil-dependent model and a TSLP-dependent model of atopic dermatitis. We will analyze the requirement of STAT6-regulated genes in various hematopoietic cell types, endothelial cells or epithelial cells and keratinocytes for extravasation of effector cells. We will further study how deletion of individual genes encoding integrins and other adhesion proteins in eosinophils or basophils affects their tissue migration. Finally, we will study the role of alternatively activated macrophages (AAMs) in inflammation and wound healing in lung and skin using our newly generated AAN fate mapping and delete mice.