CCL27-CCR10 interactions regulate T cell-mediated skin inflammation |
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Authors: | Homey Bernhard Alenius Harri Müller Anja Soto Hortensia Bowman Edward P Yuan Wei McEvoy Leslie Lauerma Antti I Assmann Till Bünemann Erich Lehto Maili Wolff Henrik Yen David Marxhausen Heather To Wayne Sedgwick Jonathon Ruzicka Thomas Lehmann Percy Zlotnik Albert |
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Affiliation: | DNAX Research Institute, Palo Alto, California, USA. berhard.homey@uni-duesseldorf.de |
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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. |
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