title: CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.
abstract: 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.
authors.affiliation: DNAX Research Institute, Palo Alto, California, USA. berhard.homey@uni-duesseldorf.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Anja
authors.initials: A
authors.lastname: Müller
authors.forename: Hortensia
authors.initials: H
authors.lastname: Soto
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Leslie
authors.initials: L
authors.lastname: McEvoy
authors.forename: Antti I
authors.initials: AI
authors.lastname: Lauerma
authors.forename: Till
authors.initials: T
authors.lastname: Assmann
authors.forename: Erich
authors.initials: E
authors.lastname: Bünemann
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: David
authors.initials: D
authors.lastname: Yen
authors.forename: Heather
authors.initials: H
authors.lastname: Marxhausen
authors.forename: Wayne
authors.initials: W
authors.lastname: To
authors.forename: Jonathon
authors.initials: J
authors.lastname: Sedgwick
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Percy
authors.initials: P
authors.lastname: Lehmann
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: 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
chemical_list: 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