Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
J Invest Dermatol. 2012 Apr;132(4):1280-9. doi: 10.1038/jid.2011.470. Epub 2012 Feb 2.
LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes) is a ligand for HVEM. LIGHT-HVEM interactions are important in T helper type 1 (Th1) immune responses. In some cases with early stages of cutaneous T cell lymphoma (CTCL), IL-2, IFN-γ, and Th1 chemokines are expressed in lesional skin, while IL-4, IL-5, and Th2 chemokines are dominant in advanced CTCL. In this study, we investigated roles of LIGHT and HVEM in the microenvironment of CTCL. LIGHT enhanced production of Th1 chemokines, such as CXC chemokine ligand (CXCL) 9, CXCL10, and CXCL11, from IFN-γ-treated dermal fibroblasts via phosphorylation of inhibitor κBα. Messenger RNA levels of these chemokines were increased in lesional skin of early CTCL. Interestingly, while LIGHT expression in CTCL skin correlated with disease progression, HVEM expression was significantly decreased in advanced CTCL skin. HVEM was detected in dermal fibroblasts in early CTCL skin, but not in advanced CTCL skin in situ. These results suggest that low HVEM expression on dermal fibroblasts in advanced CTCL skin attenuates expression of Th1 chemokines, which may contribute to a shift to a Th2-dominant microenvironment as disease progresses.
LIGHT（淋巴毒素样，表达诱导，与单纯疱疹病毒糖蛋白 D 竞争疱疹病毒进入介质 (HVEM)，HVEM 是 T 淋巴细胞表达的受体）是 HVEM 的配体。LIGHT-HVEM 相互作用在辅助性 T 细胞 1（Th1）免疫反应中很重要。在皮肤 T 细胞淋巴瘤（CTCL）的早期阶段，病变皮肤中表达 IL-2、IFN-γ 和 Th1 趋化因子，而在晚期 CTCL 中 IL-4、IL-5 和 Th2 趋化因子占主导地位。在这项研究中，我们研究了 LIGHT 和 HVEM 在 CTCL 微环境中的作用。LIGHT 通过磷酸化抑制剂 κBα 增强 IFN-γ 处理的真皮成纤维细胞产生 Th1 趋化因子，如 CXCL9、CXCL10 和 CXCL11。这些趋化因子的信使 RNA 水平在早期 CTCL 的病变皮肤中增加。有趣的是，虽然 LIGHT 在 CTCL 皮肤中的表达与疾病进展相关，但 HVEM 在晚期 CTCL 皮肤中的表达显著降低。HVEM 在早期 CTCL 皮肤的真皮成纤维细胞中检测到，但在晚期 CTCL 皮肤中未原位检测到。这些结果表明，晚期 CTCL 皮肤真皮成纤维细胞中 HVEM 的低表达减弱了 Th1 趋化因子的表达，这可能导致疾病进展时向 Th2 优势微环境的转变。
