Our research focusses on the role of dendritic cells (DCs) and myeloid cells in immune homeostasis. DCs are spread all over the body and form dense cellular networks in enovironment exposed tissues such as epithelial layers of lung, intestine and skin. They are regarded as the cellular outposts of the immune system. They are equipped with a variety of receptor structures for environmental molecules and microbes and are capable of migrating to lymphoid tissues, where they induce antigen-specific T-cell responses. How they integrate environmental signals for inducing proper immune responses to harmful pathogens and at the same time prevent inappropriate/overshooting immune responses to harmless antigens is still poorly understood. Dysregulation of DC-mediated immune homeostasis might lead to the initiation and perpetuation of autoimmune/inflammatory diseases and might be critically involved in tumor immune escape. Importantly, the DC system comprises several family members that markedly differ in phenotype and function. Hence, DC hetereogeneity might represent a key functional determinant of immunhomeostasis. Langerhans cells (LC) in the epidermis seem to be specialized in exerting a tolgerogenic function and to induce innate anti-viral immunity, whereas interstital DCs in the dermis might be of key importance for inducing protective anti-microbial immunity. We previously demonstrated that LC differentiation from human progenitor cells is critically dependent on TGF-β1, a prototypical anti-inflammatory cytokine produced by epithelial cells. TGF-β1 or structurally related molecules of the bone morphogenetic protein (BMP) family instruct precursors to acquire LC characteristics and to induce molecules that allow LCs to exert a tolerogenic function. We aim to understand the molecular mechanisms underyling TGF-β1/BMP-dependent induction of LCs from shared DC precursors and which molecular pathways in LCs might allow these cells to secure tolerance to epithelial and envirtonmental signals. We employ a variety of experimental methods for studying the human and murine immune system. A better understanding of these processes might lead to the establishement of novel therapeutic strategies for a variety of medical conditions including autimmune/inflammatory/allergic diseases, organ/cell transplantation and cancer.

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