Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells
Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells
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DOI：
10.1016/j.jaci.2007.01.003
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发表时间：
2007-04-01
影响因子：
14.2
通讯作者：
Romani, Nikolaus
中科院分区：
文献类型：
--
作者：
Ebner, Susanne;Nguyen, Van Anh;Romani, Nikolaus
背景资料：胸腺基质淋巴细胞生成素（Thymic stromal lymphopoietin，TSLP）可使人外周血CD 11 c（+）树突状细胞（Dendritic cells，DC）具有诱导促变应性T细胞的能力。TSLP以高水平存在于特应性皮炎的表皮中，在那里它似乎触发表皮朗格汉斯细胞（LC）的迁移;然而，关于TSLP对LC的影响还不清楚。目的：方法：采用胰蛋白酶消化法从健康人皮肤中分离LCs，免疫磁珠法（CD 1a）富集LCs，体外培养2 d。此外，迁移LC从表皮sheets 3 day.Results：除了TSLP促进生存和成熟的LC获得胰蛋白酶消化，其表达增加的CD 83，CD 86，和高水平的MHC 11。TSLP显著增加了迁移性LC的数量。与迁移性TSLP-LC共培养的同种异体初始CD 4（+）T细胞产生较少的IFN-γ和IL-10，以及较多的IL-4、IL-5、IL-13和TNF-α。最后，TSLP-LCs分泌显着更多的T（H）2 T细胞吸引趋化因子CCL 17/thymus和活化调节趋化因子。他们强调了TSLP对表皮LC的直接影响。临床意义：我们的数据强调了LC在特应性皮炎的触发中的关键作用。此外，他们强调了TSLP作为特应性疾病的潜在治疗靶点的兴趣。
Background: 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. Objective: Effects of TSLP on human epidermal LCs were investigated.Methods: 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.Results: 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 11. TSLP markedly increased numbers of migratory LCs. Allogeneic naive 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.Conclusion: These cytokine patterns correspond to those described for TSLP-treated blood DCs. They highlight a direct effect of TSLP on epidermal LCs. Clinical implications: 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.