E-Selectin, Thymus- and Activation-Regulated Chemokine/CCL17, and Intercellular Adhesion Molecule-1 Are Constitutively Coexpressed in Dermal Microvessels: A Foundation for a Cutaneous Immunosurveillance System

• Published in: The Journal of immunology (1950) 2004-02, Vol.172 (3), p.1575-1581
• Main Authors: Chong, Benjamin F, Murphy, Jo-Ellen, Kupper, Thomas S, Fuhlbrigge, Robert C
• Format: Article
• Language: English
• Subjects: CCL17 protein; Cell Movement - immunology; Chemokine CCL17; Chemokines, CC - biosynthesis; Chemokines, CC - metabolism; Chemokines, CC - physiology; Confocal multicolor immunofluorescence imaging; E-Selectin - biosynthesis; E-Selectin - metabolism; E-Selectin - physiology; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Humans; Immunohistochemistry; Immunologic Memory; intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - metabolism; Intercellular Adhesion Molecule-1 - physiology; LFA-1 antigen; Lymphocyte Activation - immunology; Microcirculation - immunology; Microcirculation - metabolism; Microscopy, Fluorescence; Models, Immunological; Monitoring, Immunologic; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Skin - blood supply; Skin - immunology; Skin - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.3.1575

The success of the cutaneous immune system reflects its ability to rapidly and efficiently recruit leukocytes to areas of trauma and infection. Skin-homing memory T cells expressing cutaneous lymphocyte-associated Ag tether on the walls of postcapillary venules in inflamed skin via interaction with endothelial E-selectin and roll in response to the shear stress imparted by flowing blood. Rolling cells sample the vascular surface for chemoattractant compounds (e.g., thymus- and activation-regulated chemokine/CCL17 interacting with CCR4 on the leukocyte surface) and, if successfully stimulated, progress to firm arrest and transmigration mediated by LFA-1 and vascular ICAM-1. Although it is established that this sequence of events draws T cells into inflamed skin, the mechanisms directing trafficking of T cells to noninflamed skin are less well characterized. We hypothesized that basal expression and colocalization of E-selectin, chemokine (e.g., CCL17), and ICAM-1 in dermal vessels could serve to recruit T cells to noninflamed human skin. Immunohistochemical staining for E-selectin and CD31 demonstrated E-selectin expression in a restricted subset of dermal vessels in noninflamed human skin from three different sites. Confocal multicolor immunofluorescence imaging revealed a nonuniform distribution of E-selectin in dermal vessels as well as colocalization of E-selectin with CCL17 and ICAM-1. Coexpression of these molecules on blood vessels in noninflamed skin provides the basis for a model of cutaneous immunosurveillance system active in the absence of pathologic inflammation.