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.
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.
Chong
Benjamin F
BF
Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Murphy
Jo-Ellen
JE
Kupper
Thomas S
TS
Fuhlbrigge
Robert C
RC
D002465:Cell Movement / Q000276:immunology; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D019040:E-Selectin / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008833:Microcirculation / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018448:Models, Immunological; D015166:Monitoring, Immunologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1