Langerhans cells require signals from both tumour necrosis factor-alpha and interleukin-1 beta for migration
Langerhans cells require signals from both tumour necrosis factor-alpha and interleukin-1 beta for migration
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DOI：
10.1046/j.1365-2567.1997.00360.x
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发表时间：
1997-11-01
期刊：
影响因子：
6.4
通讯作者：
Kimber, I
中科院分区：
文献类型：
--
作者：
Cumberbatch, M;Dearman, RJ;Kimber, I
接触致敏的诱导阶段与表皮朗格汉斯细胞（LC）从皮肤的运动和它们的迁移有关，通过传入淋巴，到引流淋巴结，在那里它们作为免疫刺激树突状细胞（DC）积累。先前已经证明，肿瘤坏死因子- α (tnf - α)为LC迁移提供了一个重要信号，并且在缺乏该细胞因子的情况下，LC从表皮向区域淋巴结的移动受到抑制。最近的证据表明，白细胞介素-1 β (IL-1 β)，一种在小鼠表皮中仅由LC产生的细胞因子，也可能在LC迁移中发挥作用。本文研究的目的是利用相关的中和性抗细胞因子抗体，阐明tnf - α和IL-1 β对LC从表皮迁移的作用。研究发现，与抗tnf - α一样，在接触性过敏原恶唑酮致敏之前，对小鼠进行全身注射（通过腹腔注射）抗il -1 β，可显著抑制DC在引流淋巴结中的积累。研究还表明，抗IL-1 β抑制tnf - α诱导的LC迁移和DC积累，同样，IL-1 β诱导的LC迁移和DC积累的刺激被先前的抗tnf - α治疗所削弱。基于这些数据，我们提出刺激LC迁移以响应皮肤致敏需要LC接收两个独立的信号，一个由tnf - α提供，另一个由IL-1 β提供。形态学分析表明，tnf - α和IL-1 β诱导的LC的变化可能包括粘附分子的表达改变，以及获得与基底膜相互作用和通过基底膜的能力。
The induction phase of contact sensitization is associated with the movement of epidermal Langerhans cells (LC) from the skin and their migration, via afferent lymphatics, to draining lymph nodes where they accumulate as immunostimulatory dendritic cells (DC). It has been demonstrated previously that tumour necrosis factor-alpha (TNF-alpha) provides an important signal for LC migration and that in the absence of this cytokine, movement of LC from the epidermis to regional lymph nodes is inhibited. Recent evidence indicates that interleukin-1 beta (IL-1 beta), a cytokine produced in murine epidermis exclusively by LC, may also play a role in LC migration. The purpose of the investigations described here was to clarify, using relevant neutralizing anticytokine antibodies, the contributions made by TNF-alpha and IL-1 beta to the migration of LC from the epidermis. It was found that like anti-TNF-alpha, anti-IL-1 beta administered systemically to mice (by intraperitoneal injection), prior to skin sensitization with the contact allergen oxazolone, resulted in a marked inhibition of DC accumulation in draining lymph nodes. It was shown also that anti-IL-1 beta inhibited TNF-alpha-induced LC migration and DC accumulation and that, in similar fashion, the stimulation of LC migration and DC accumulation induced by IL-1 beta was compromised by prior treatment with anti-TNF-alpha. Based upon these data it is proposed that the stimulation of LC migration in response to skin sensitization requires the receipt by LC of two independent signals, one provided by TNF-alpha and the other by IL-1 beta. Morphological analyses of LC in epidermal sheets prepared from animals exposed to these cytokines with or without prior systemic treatment with anti-cytokine antibody suggested that the changes induced in LC by TNF-alpha and IL-1 beta may include the altered expression of adhesion molecules and acquisition of the ability to interact with and pass through the basement membrane.