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
DNAX Research Institute, Palo Alto, California, USA.
Nat Med. 2002 Feb;8(2):157-65. doi: 10.1038/nm0202-157.
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.
皮肤相关趋化因子CCL27（也称为CTACK、ALP和ESkine）及其受体CCR10（GPR - 2）在体外介导归巢至皮肤的T细胞的趋化反应。我们在此报告，患有银屑病、特应性皮炎或过敏性接触性皮炎的患者中，大多数浸润皮肤的淋巴细胞表达CCR10。表皮基底角质形成细胞产生与细胞外基质结合、介导黏附并呈现在真皮内皮细胞表面的CCL27蛋白。肿瘤坏死因子 - α和白细胞介素 - 1β诱导CCL27的产生，而糖皮质激素丙酸氯倍他索则抑制其产生。循环中归巢至皮肤的CLA + T细胞、真皮微血管内皮细胞和成纤维细胞在其细胞表面表达CCR10。在体内，皮内注射CCL27可吸引淋巴细胞，相反，中和CCL27 - CCR10相互作用会损害淋巴细胞向皮肤的募集，导致变应原诱导的皮肤炎症受到抑制。总之，这些发现表明CCL27 - CCR10相互作用在T细胞介导的皮肤炎症中起关键作用。
