Tumour necrosis factor-α-induced migration of human Langerhans cells:: the influence of ageing
Tumour necrosis factor-α-induced migration of human Langerhans cells:: the influence of ageing
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DOI：
10.1046/j.1365-2133.2002.04549.x
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发表时间：
2002-01-01
影响因子：
10.3
通讯作者：
Griffiths, CEM
中科院分区：
文献类型：
--
作者：
Bhushan, M;Cumberbatch, M;Griffiths, CEM
背景郎格汉斯细胞(LCs)携带抗原从表皮成功迁移至引流淋巴结，在皮肤免疫反应的启动和调节中发挥重要作用。肿瘤坏死因子-α是一种角质形成细胞来源的细胞因子，最近被证明在动员人类表皮细胞的LC中起着重要作用。目的探讨年龄对肿瘤坏死因子-α诱导LC迁移能力的影响。方法10名老年志愿者(男性6名，女性4名，平均年龄72-79岁)和青年志愿者10名(男性6名，女性4名；平均年龄23岁，年龄18-35岁)，分别在光保护臀部皮肤的两对部位皮内注射200U稀释于无菌生理盐水中的重组人肿瘤坏死因子-α，并在对照部位注射无菌生理盐水。两小时后，通过穿孔活检切除成对的注射部位。在准备表皮薄片和免疫荧光染色LC标记物CD1a之后，对一组配对的活检组织进行了评估，以评估表皮LC的频率和形态。结果青年组和老年组表皮层LC的平均+/-扫描电子显微镜基线值分别为1156.3+/-38.5cell mm(-2)和835.7+/-48.2cell mm(-2)，P<；皮内注射200U的肿瘤坏死因子-α可显著降低老年人和青年受试者腰腿痛的发生率(P<；0.01)。然而，肿瘤坏死因子-α诱导的LC迁移的程度在两组之间有很大的不同，老年志愿者LC频率平均减少9%，而年轻受试者平均减少23%。在所有年轻受试者中，暴露于肿瘤坏死因子-α与血管周围多形核浸润有关；相反，只有50%的老年人表现出这种反应。结论年轻和老年皮肤在静息LC数和对肿瘤坏死因子-α的反应方面存在显著差异。这些与年龄相关的LC频率和功能的变化可能是老年人皮肤免疫功能改变的原因之一。
Background Langerhans cells (LCs) play essential roles in the initiation and regulation of cutaneous immune responses mediated through their successful migration from the epidermis to draining lymph nodes while carrying antigen. Tumour necrosis factor (TNF)-alpha, a keratinocyte-derived cytokine, has recently been shown to play an important role in the mobilization of LCs from human epidermis. Although it is known that with age the immune system changes, the influence of increasing age on the function of human LCs has not been defined clearly.Objectives To examine the influence of age on the ability of TNF-alpha to induce LC migration.Methods Ten elderly (six men, four women; mean age 76 years, range 72-79) and 10 young (six men, four women; mean age 23 years, range 18-35) volunteers received intradermal injections of 200 U of human recombinant TNF-alpha diluted in sterile saline, and control injections of sterile saline alone, at each of two paired sites identified on photoprotected buttock skin. Two hours later, paired injection sites were excised by punch biopsy. One set of paired biopsies was processed for assessment of the frequency and morphology of epidermal LCs, following preparation of epidermal sheets and immunofluorescence staining for the LC marker CD1a. The remaining paired biopsies were processed in formalin and the inflammatory response to TNF-alpha was assessed by standard histological examination.Results Mean +/- SEM baseline values for LC frequency within epidermal sheets were significantly different between young (1156.3 +/- 38.5 cells mm(-2)) and elderly subjects (835.7 +/- 48.2 cells mm(-2); P < 0.01). Intradermal injections of 200 U of TNF-α caused a significant reduction in the frequency of LCs in both elderly and young subjects (P < 0.01). However, the extent of TNF-alpha-induced LC migration was substantially different between the two groups, with a mean 9% reduction in LC frequency in elderly volunteers compared with a mean 23% decrease in young subjects. Exposure to TNF-alpha was associated with a perivascular polymorphonuclear infiltrate at 2 11 in all young subjects; in contrast, only 50% of the elderly individuals showed evidence of such a response,Conclusions There are significant differences between young and old skin with respect to both resting LC numbers and their response to TNF-alpha. These age-related changes In LC frequency and function may contribute to the altered cutaneous immune function observed in the elderly.