Cumberbatch Marie, Singh Minal, Dearman Rebecca J, Young Helen S, Kimber Ian, Griffiths Christopher E M
Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, SK10 4TJ, England, UK.
J Exp Med. 2006 Apr 17;203(4):953-60. doi: 10.1084/jem.20052367. Epub 2006 Mar 27.
We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor alpha [TNF-alpha], and interleukin-1beta [IL-1beta]) was largely absent, despite the fact that treatment with TNF-alpha and IL-1beta was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1beta or TNF-alpha that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis.
我们研究了银屑病是否与对表皮朗格汉斯细胞(LC)功能的全身影响相关,特别是LC从皮肤的迁移。与正常皮肤相比,银屑病患者未受累皮肤中表皮LC的频率和形态正常。然而,尽管TNF-α和IL-1β治疗在患者和对照组中引发了类似的炎症反应,但这些细胞对通常诱导迁移的刺激(化学变应原、肿瘤坏死因子α [TNF-α]和白细胞介素-1β [IL-1β])的动员在很大程度上不存在。未受累皮肤中LC迁移失败并非归因于动员所需的IL-1β或TNF-α受体表达改变,也与诱导的皮肤细胞因子表达无关。尽管尚未正式排除LC迁移/更新动力学改变的作用,但这些数据揭示了银屑病中LC功能非常一致的减退,这可能在疾病发病机制中起决定性作用。