CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.
The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.
Homey
Bernhard
B
DNAX Research Institute, Palo Alto, California, USA. berhard.homey@uni-duesseldorf.de
Alenius
Harri
H
Müller
Anja
A
Soto
Hortensia
H
Bowman
Edward P
EP
Yuan
Wei
W
McEvoy
Leslie
L
Lauerma
Antti I
AI
Assmann
Till
T
Bünemann
Erich
E
Lehto
Maili
M
Wolff
Henrik
H
Yen
David
D
Marxhausen
Heather
H
To
Wayne
W
Sedgwick
Jonathon
J
Ruzicka
Thomas
T
Lehmann
Percy
P
Zlotnik
Albert
A
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D018613:Microscopy, Confocal; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
C492276:CCL27 protein, human; C515706:CCR10 protein, human; C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; D054425:Chemokine CCL27; D019742:Chemokines, CC; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing