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. Finally, we have shown that mast cells express CX3CR1, a receptor for the unique membrane-bound chemokine termed fractalkine. In vitro, mast cells respond to fractalkine in chemotaxis assays but are not stimulated to release preformed mediators. By immunohistochemical techniques, we have shown expression of fractalkine in populations of cells in skin where mast cells are known to accumulate. Thus, we have proposed that fractalkine participates in the anatomic localization of mast cells at immunologically critical sites of the skin including blood vessels and near dendritic cells.
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