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-α and interleukin-1β 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.