""""""""The lab is focused on elucidating important aspects of Langerhans cell biology, particularly those that relate to Langerhans cell differentiation, trafficking and activation. To faciliate these studies we have identified culture conditions that permit Langerhans cell-like cells to be expanded from murine fetal skin and extensively characterized them. In preliminary studies, we determined that fetal skin-derived dendritic cells and Langerhans cells exhibit a similar surface phenotype and possess similar functional activity. In addition, the dendritic cells propagated in vitro respond to the same spectrum of inflammatory mediators (IL-1, TNF and LPS) that activate dendritic cells in vivo. In more recent studies, we have characterized the response of fetal skin-derived dendritic cells to immunostimulatory oligodeoxynucleotides (in collaboration with Dr. Jonathan Vogel) and Leishmania major. The results of these experiments indicate that both immunostimulatory oligodeoxynucleotides and Leishmania activate dendritic cells inducing them to upregulate cell surface MHC and costimulatory molecules and to produce the Th1-promoting cytokine IL-12. In ongoing studies, we are continuing to study Leishmania-dendritic cell interactions. We have also initiated studies of matrix metalloprotease production and function in Langerhans cell-like dendritic cells and studies of patterns of gene expression in activated Langerhans cells.""""""""
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