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- Title
CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.
- 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
- 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.
- Publication
Nature medicine, 2002, Vol 8, Issue 2, p157
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm0202-157