An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin.
An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin.
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朗格汉斯细胞衍生的 IL-1 beta 在皮肤初级免疫反应的启动中发挥着重要作用。
DOI：
10.4049/jimmunol.150.9.3698
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发表时间：
1993
影响因子：
4.4
通讯作者：
S. Katz
中科院分区：
文献类型：
--
作者：
A. Enk;V. Angeloni;M. Udey;S. Katz
朗格汉斯细胞（LC）是皮肤中诱导初级免疫应答所需的Ag呈递细胞。在被Ag激活后，LC表达增加的MHC II类Ag水平，表现出增加的辅助细胞活性，并迁移到局部淋巴结，在那里它们刺激T细胞。LC活化的最早表现之一是在体内暴露于接触性过敏原后15分钟内LC中IL-1 β mRNA的积累量增加。为了确定LC增强的IL-1 β产生是否与表皮致敏有因果关系，我们将IL-1 β皮内注射到BALB/c小鼠的耳中，并在4小时后提取总表皮RNA。采用定量逆转录酶-聚合酶链反应技术比较皮内注射IL-1 β与皮内注射IL-1 α或TNF α或局部应用接触性变应原三硝基氯苯（3% TNCB）引起的IL-1 α、IL-1 β、巨噬细胞炎性蛋白2、IL-10、TNF-α和1-A α链mRNA信号变化。皮内注射25 ng IL-1 β导致IL-1 α、IL-1 β、MIP-2、IL-10、TNF α和II类I-A α的mRNA信号增强5- 100倍，模拟过敏原引起的变化。相比之下，注射等量的IL-1 α或TNF α不会显著改变表皮细胞因子模式。模拟局部应用TNCB的作用，皮内注射IL-1 β（而不是IL-1 α或TNF α）也引起LC MHC II类表达的增强。此外，在抗CD 3增殖测定中，来自IL-1 β注射皮肤的LC比来自IL-1 α或假注射皮肤的LC更有效2至3倍。最后，在TNCB处理前将仓鼠抗mIL-1 β mAb注射到皮肤中完全防止了对该过敏原的致敏，尽管注射相似量的仓鼠抗mIL-1 α mAb或PBS没有效果。综上所述，我们的数据表明，树突状细胞衍生的IL-1 β可能是启动皮肤初级免疫反应所需的关键分子。
Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1-A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell-derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin.