TY - JOUR
T1 - E-Selectin, Thymus- and Activation-Regulated Chemokine/CCL17, and Intercellular Adhesion Molecule-1 Are Constitutively Coexpressed in Dermal Microvessels
T2 - A Foundation for a Cutaneous Immunosurveillance System
AU - Chong, Benjamin F.
AU - Murphy, Jo Ellen
AU - Kupper, Thomas S.
AU - Fuhlbrigge, Robert C.
PY - 2004/2/1
Y1 - 2004/2/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.172.3.1575
DO - 10.4049/jimmunol.172.3.1575
M3 - Article
C2 - 14734737
AN - SCOPUS:1542749410
SN - 0022-1767
VL - 172
SP - 1575
EP - 1581
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -