Department of Dermatology, University Hospital of the Technical University Dresden, Dresden, Germany.
Am J Pathol. 2011 Sep;179(3):1434-42. doi: 10.1016/j.ajpath.2011.05.040. Epub 2011 Jul 8.
Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163(+) CD209(+) macrophages at the invasive margin of the tumor and not expressed by mature CD208(+) dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis of CTCL.
蕈样肉芽肿(MF)是最常见的皮肤 T 细胞淋巴瘤(CTCL),可在数年内从斑片期进展为真皮肿瘤和全身性受累。皮肤中的趋化因子与 CTCL 细胞的相互作用可能对疾病的发病机制有影响。在这项研究中,我们通过 PCR 分析和免疫荧光染色显示,趋化因子 CCL18 存在于 MF 患者和其前驱形式斑块状副银屑病的皮肤活检标本中,但不存在于健康组织中。此外,MF 患者的 CCL18 血清水平比健康对照组高三倍。在皮肤中,CCL18 特异性表达于肿瘤侵袭边缘的 CD163(+) CD209(+)巨噬细胞,而不表达于肿瘤中心的成熟 CD208(+)树突状细胞。相比之下,趋化因子 CCL17 广泛表达。此外,CCL18 促进 CTCL 细胞的趋化而不促进其增殖。CCL18 抑制肿瘤细胞的增殖,并消除 CXCL12 诱导的 CTCL 细胞系的生长。这些数据将 CCL18 的高表达与 CTCL 联系起来,并提示趋化因子在 CTCL 发病机制中具有免疫调节作用。