CCL1-CCR8 interactions:: An axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation
CCL1-CCR8 interactions:: An axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation
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DOI：
10.4049/jimmunol.174.8.5082
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Homey, B
中科院分区：
文献类型：
--
作者：
Gombert, M;Dieu-Nosjean, MC;Homey, B
特应性皮炎是一种慢性复发性皮肤病，在儿童中的患病率稳步增加，为10-20%。皮肤浸润T细胞、树突状细胞（DC）和肥大细胞被认为在其发病机制中发挥关键作用。我们报告CC趋化因子CCL 1（I-309）的表达在特应性皮炎中与银屑病、皮肤红斑狼疮或正常皮肤相比显著且选择性上调。特应性皮炎患者的CCL 1血清水平显著高于健康个体的水平。DC、肥大细胞和真皮内皮细胞在特应性皮肤炎症和过敏原激发期间是CCL 1的丰富来源，并且金黄色葡萄球菌衍生的产物诱导其产生。在体外，肥大细胞上的IgE的结合和交联导致这种炎性趋化因子的显著上调。其特异性受体CCR 8在循环T细胞的一小部分上表达，并在间质DC、体外产生的朗格汉斯细胞及其单核细胞前体上大量表达。尽管DC在成熟过程中保持其CCR 8（+）状态，但循环T细胞的短暂激活会将CCR 8从胞浆内储存募集到细胞表面。此外，炎性和特应性相关趋化因子CCL 1与稳态趋化因子CXCL 12（SDF-1 α）协同作用，导致T细胞和朗格汉斯细胞样DC的募集。总之，这些发现表明，轴CCL 1-CCR 8链接的适应性和先天免疫功能，在特应性皮肤炎症的启动和放大中发挥作用。
Atopic dermatitis represents a chronically relapsing skin disease with a steadily increasing prevalence of 10-20% in children. Skin-infiltrating T cells, dendritic cells (DC), and mast cells are thought to play a crucial role in its pathogenesis. We report that the expression of the CC chemokine CCL1 (I-309) is significantly and selectively up-regulated in atopic dermatitis in comparison to psoriasis, cutaneous lupus erythematosus, or normal skin. CCL1 serum levels of atopic dermatitis patients are significantly higher than levels in healthy individuals. DC, mast cells, and dermal endothelial cells are abundant sources of CCL1 during atopic skin inflammation and allergen challenge, and Staphylococcus aureus-derived products induce its production. In vitro, binding and cross-linking of IgE on mast cells resulted in a significant up-regulation of this inflammatory chemokine. Its specific receptor, CCR8, is expressed on a small subset of circulating T cells and is abundantly expressed on interstitial DC, Langerhans cells generated in vitro, and their monocytic precursors. Although DC maintain their CCR8(+) status during maturation, brief activation of circulating T cells recruits CCR8 from intracytoplamic stores to the cell surface. Moreover, the inflammatory and atopy-associated chemokine CCL1 synergizes with the homeostatic chemokine CXCL12 (SDF-1 alpha) resulting in the recruitment of T cell and Langerhans cell-like DC. Taken together, these findings suggest that the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation.