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
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作者:
Chong, BF
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机构:Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
Chong, BF
Murphy, JE
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机构:Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
Murphy, JE
Kupper, TS
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机构:Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
Kupper, TS
Fuhlbrigge, RC
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机构:Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
Fuhlbrigge, RC
机构:
[1] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
[2] Johns Hopkins Sch Med, Baltimore, MD 21205 USA
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.
机构:
Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Berin, MC
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Eckmann, L
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Eckmann, L
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Broide, DH
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Broide, DH
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Kagnoff, MF
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
机构:
Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Berin, MC
;
Eckmann, L
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Eckmann, L
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Broide, DH
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA
Broide, DH
;
Kagnoff, MF
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Univ Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Med, Lab Mucosal Immunol 0623D, La Jolla, CA 92093 USA