A properly functioning skin immune system is essential to protect this large organ from pathogen entry and tumor cell outgrowth. Many skin diseases are characterized by dysregulation of the immune response. My goal is to understand the mechanisms of the innate and adaptive immune responses in the skin in order to explain the immunopathology of inflammatory skin disorders, such as psoriasis. To this aim both clinical and basic research is performed, using skin specimens from patients and healthy volunteers. One of the research lines focuses on cutaneous dendritic cells: epidermal Langerhans cells and dermal dendritic cell subsets. These cells are isolated from human skin specimens or generated from monocytes using special cocktails of cytokines. Dendritic cells activate T cells and regulate their effector-function via a complex array of co-stimulatory and polarizing signals. These signals expressed by dendritic cells are quite flexible and dependent on micro-environmental circumstances. The aim is to determine the phenotypical and functional characteristics of these dendritic cell subsets and to understand how these properties can manipulated. With this knowledge it may be possible to render dendritic cells suitable as vaccine-based adjuvants, for instance to establish or break tolerance. Another line of research focuses on the pathogenesis of psoriasis and encompasses the determination of the number, distribution, and state of activation of different cell types, as well as the presence of inflammatory mediators in lesional skin. In addition, cells (e.g. T cells, dendritic cells) are isolated from psoriatic lesional skin to study their function in order to determine abbarations as compared to their counterparts in healthy skin. Better understanding of the inflammatory processes involved in the development of psoriasis may lead to the identification of new drug targets to treat this disease.