Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Invest Dermatol. 2010 Nov;130(11):2621-8. doi: 10.1038/jid.2010.175. Epub 2010 Jul 1.
Recently the Th1/Th2 concept has been revised and Th17 cells have been implicated in allergy. Despite clear correlative evidence, the cellular and molecular basis for the connection between increased IL-17A and IgE in allergy has not been elucidated. Here we show using flow cytometry that allergic patients have higher numbers of IL-17A+ cells compared to nonallergic donors. The selective removal of IL-17A+ cells from peripheral blood mononuclear cells of allergic donors after an IL-17A secretion assay reduces IgE levels, whereas re-addition of recombinant IL-17A restores it, as measured by ELISA, showing their important functional implication for IgE production. In addition, IL-17A directly promotes the differentiation of IgE-secreting cells and IgE production upon anti-CD40/IL-4 costimulation, as shown by enzyme-linked immunospot technique and ELISA. IL-17A triggers rapid degradation of IκBα and subsequent translocation of NF-κB into the B-cell nucleus, followed by transcription of epsilon germ-line, activation-induced cytidine deaminase, and IFN regulatory factor 4, as analyzed by flow cytometry, western blot, and quantitative real-time RT-PCR, respectively. Our study shows that IL-17A+ cells promote IgE production and that IL-17A exerts its pro-allergic effect directly at the level of B cells. Therefore, IL-17A might be a target for the treatment of IgE-dependent diseases, including atopic dermatitis.
最近，Th1/Th2 概念已经得到修正，Th17 细胞被认为与过敏有关。尽管有明确的相关性证据，但尚未阐明过敏中 IL-17A 和 IgE 增加之间的细胞和分子基础。在这里，我们通过流式细胞术显示，与非过敏供体相比，过敏患者的 IL-17A+细胞数量更高。在 IL-17A 分泌测定后，从过敏供体的外周血单核细胞中选择性去除 IL-17A+细胞会降低 IgE 水平，而添加重组 IL-17A 会恢复 IgE 水平，这通过 ELISA 测量，表明它们对 IgE 产生具有重要的功能意义。此外，IL-17A 直接促进 IgE 分泌细胞的分化和 IgE 的产生在抗 CD40/IL-4 共刺激下，如酶联免疫斑点技术和 ELISA 所示。IL-17A 触发 IκBα 的快速降解，并随后使 NF-κB 转位到 B 细胞核中，随后进行 epsilon 种系转录、激活诱导的胞嘧啶脱氨酶和 IFN 调节因子 4，分别通过流式细胞术、western blot 和定量实时 RT-PCR 进行分析。我们的研究表明，IL-17A+细胞促进 IgE 的产生，并且 IL-17A 在 B 细胞水平上发挥其促过敏作用。因此，IL-17A 可能是 IgE 依赖性疾病（包括特应性皮炎）治疗的靶点。
