Immune cells including T cells and antigen-presenting dendritic cells (DCs) migrate to and from the skin as part of the normal processes of immune surveillance and protection. Chemokines comprise a large family of protein that are intimately involved in recruiting these immune cells into peripheral tissues such as skin and in compartmentalizing them in certain regions of secondary lymphoid organs such as lymph nodes (LN). Over the last year, we have shown that skin dendritic cells express the chemokine receptor CXCR5 as they mature. In vitro, skin DCs respond to the CXCR5 ligand, BLC, in chemotaxis assays. In vivo, skin DCs appear to be able to partially home to B cell areas of the LN. T cells migrate into skin during immune responses by first binding to microvascular endothelial cells in the skin. Using a system comprised of cultured human dermal microvascular endothelial cells (HDMEC), we have shown that HDMEC strongly express message for a CCR6-ligand termed LARC. Interestingly, a discrete subset of skin-homing T cells express CCR6. Using a parallel plate flow chamber system, we have demonstrated that CCR6 appears to be critical for the firm adherence of memory T cells to activated HDMEC under physiologic flow conditions. Our previous studies have shown that the chemokine, CCL21, and its receptor (CCR7) found on activated dendritic cells (DC), plays a critical role in the entry of DC in lymphatic vessels in which CCL21 is constitutively synthesized by lymphatic endothelial cells. We have now shown that transduction of murine melanoma with CCR7 enables these CCR7-expressing cells to metastasize over 500-fold better at early time points to regional draining lymph nodes via afferent lymphatic vessels. Thus, we raise the possibility that melanoma and perhaps other cancers can express certain chemokine receptors which enable them to metastasize more efficiently in vivo.
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