Toxicology Group, Faculty of Life Sciences, University of Manchester, Manchester, UK.
Clin Exp Dermatol. 2012 Jan;37(1):40-7. doi: 10.1111/j.1365-2230.2011.04172.x. Epub 2011 Sep 20.
Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis.
To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs).
CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1β (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array.
CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro.
These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment.
在早期发病的银屑病患者未受累皮肤中，表皮朗格汉斯细胞（LC）对白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的细胞因子的迁移反应受损。
使用已建立的单核细胞衍生的 LC 样细胞（mLC）模型，研究这种损伤是否反映了树突状细胞（DC）的全身性缺陷。
从银屑病患者和健康对照志愿者中分离出 CD14+单核细胞，在细胞因子鸡尾酒中培养 5 天以促进其分化为 mLC，然后用 TNF-α、IL-1β（均为 100ng/mL）或单独的培养基刺激 24 小时。通过流式细胞术定量细胞表面蛋白表达，并通过 Transwell 迁移测定评估细胞迁移到补充有 C-C 基序趋化因子（CCL）19 的培养基的能力。通过细胞因子阵列分析上清液中细胞因子和趋化因子的含量。
CD14+细胞获得了 LC 样表型，高表达 CD1a 和主要组织相容性复合体（MHC）II 类。从银屑病患者和健康对照者分离的 mLC 之间，在激活标志物的表达或细胞因子的分泌方面没有差异。此外，两组分离的 mLC 均表现出相当的体外迁移能力。
这些数据表明，银屑病患者 LC 对刺激的迁移反应失败不是归因于 DC 功能的全身性缺陷，而是反映了表皮微环境的局部变化。
