""""""""Dendritic cells (DCs) in skin and other tissues play major roles in the presentation of antigen to T cells. Chemokines are small molecules produced by a variety of cells and induce migration in cells expressing appropriate receptors. We wish to understand the role chemokines and chemokine receptors in biology of DC trafficking and function. Most of our studies are conducted with bona fide DCs derived after culturing mouse skin for several days. DCs spontaneously migrate from skin and into media where they can be collected. We perform a variety of assays including: chemotaxis assays, RT-PCR gene expression analysis, and fluorescence microscopy. We have found that CC chemokine receptor 7 (CCR7) is strongly upregulated in skin DC following exposure to inflammatory cytokines. Secondary lymphoid-tissue chemokine (SLC), a ligand of CCR7, was found to be constitutively expressed by dermal lymphatic endothelium and was highly potent in stimulating mature DC migration in vitro. Using antibodies directed against SLC, we found that DC trafficking from peripheral tissue to regional lymph nodes could be significantly inhibited in a murine model of DC trafficking, thus providing evidence the SLC and CCR7 play a functional role in the trafficking of DC to secondary lymphoid organs. We have also found that maturing DCs produce a variety of chemokines including fractalkine, the lone member of the CX3C family of chemokine. Expression of fractalkine was enhanced by ligation of CD40 on DC, suggesting a mechanism by which CD40 ligation primes DC to become better antigen presenting cells. Although initially expressed in a surface bound form, fractalkine can be cleaved from the cell surface, and the cleaved form induces migration of IL-2 stimulated T cells. Because of the unique surface bound stucture of fractalkine on the DC, it is possible that fractalkine acts as a cell surface adhesion molecule in addition to possibly acting as a T cell chemoattractant for the DC.""""""""
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