Ebner Susanne, Nguyen Van Anh, Forstner Markus, Wang Yui-Hsi, Wolfram Dolores, Liu Yong-Jun, Romani Nikolaus
Department of Dermatology and Venereology, Kompetenzzentrum Medizin Tirol, Innsbruck, Austria.
J Allergy Clin Immunol. 2007 Apr;119(4):982-90. doi: 10.1016/j.jaci.2007.01.003. Epub 2007 Feb 22.
Thymic stromal lymphopoietin (TSLP) endows human CD11c(+) dendritic cells (DCs) from peripheral blood with the capacity to induce proallergic T cells. TSLP is present at high levels in the epidermis of atopic dermatitis where it appears to trigger emigration of epidermal Langerhans cells (LCs); however, nothing else is known about the influence of TSLP on LCs.
Effects of TSLP on human epidermal LCs were investigated.
LCs were isolated by trypsinization from healthy human skin, highly enriched by immunomagnetic techniques (via CD1a) and cultured for 2 days. Additionally, migratory LCs were obtained by emigration from epidermal sheets for 3 days.
The addition of TSLP promoted survival and maturation of LCs obtained by trypsinization, as indicated by their increased expression of CD83, CD86, and high levels of MHC II. TSLP markedly increased numbers of migratory LCs. Allogeneic naïve CD4(+) T cells, cocultured with migratory TSLP-LCs produced less IFN-gamma and IL-10 and more IL-4, IL-5, IL-13, and TNF-alpha. Finally, TSLP-LCs secreted markedly more of the T(H)2 T-cell-attracting chemokine CCL17/thymus and activation-regulated chemokine.
These cytokine patterns correspond to those described for TSLP-treated blood DCs. They highlight a direct effect of TSLP on epidermal LCs.
Our data emphasize a critical role for LCs in the triggering of atopic dermatitis. Furthermore, they underscore the interest in TSLP as a potential therapeutic target in atopic diseases.
胸腺基质淋巴细胞生成素（TSLP）赋予外周血中的人CD11c(+)树突状细胞（DCs）诱导促过敏性T细胞的能力。TSLP在特应性皮炎的表皮中含量很高，似乎能触发表皮朗格汉斯细胞（LCs）的迁移；然而，关于TSLP对LCs的影响，其他方面尚不清楚。
研究TSLP对人表皮LCs的影响。
通过胰蛋白酶消化从健康人皮肤中分离LCs，通过免疫磁珠技术（通过CD1a）进行高度富集，并培养2天。此外，通过从表皮片迁移3天获得迁移性LCs。
添加TSLP可促进通过胰蛋白酶消化获得的LCs的存活和成熟，这表现为它们CD83、CD86表达增加以及高水平的MHC II。TSLP显著增加了迁移性LCs的数量。与迁移性TSLP-LCs共培养的同种异体初始CD4(+) T细胞产生的IFN-γ和IL-10较少，而IL-4、IL-5、IL-13和TNF-α较多。最后，TSLP-LCs分泌的T(H)2 T细胞吸引趋化因子CCL17/胸腺和活化调节趋化因子明显更多。
这些细胞因子模式与TSLP处理的血液DCs中描述的模式一致。它们突出了TSLP对表皮LCs的直接作用。
我们的数据强调了LCs在特应性皮炎触发中的关键作用。此外，它们强调了将TSLP作为特应性疾病潜在治疗靶点的意义。
