Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice
Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice
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DOI：
10.1016/j.jconrel.2005.08.014
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发表时间：
2005-11-28
影响因子：
10.8
通讯作者：
Aramaki, Y
中科院分区：
文献类型：
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作者：
Inoue, J;Yotsumoto, S;Aramaki, Y
CpG-寡脱氧核苷酸 (CpG-ODN) 通过增强 Th1 反应和抑制 Th2 反应在免疫中发挥关键作用。我们通过评估细胞因子和 Ig 同种型的产生，研究了 CpG-ODN 对应用于胶带剥离小鼠皮肤的抗原的免疫反应的影响。共聚焦激光扫描显微镜显示模型抗原、OVA 和 CpG-ODN 很容易穿透胶带剥离的皮肤。将 CpG-ODN 和 OVA 共同施用到受损皮肤上，引发了抗原特异性 Th1 为主的免疫反应，并增强了 Th1 型细胞因子、IL-12 和 IEN-gamma 的产生。另一方面，Th2型细胞因子IL-4的产生被急剧抑制。引流淋巴结中 mRNA 的表达支持细胞因子的产生。在抗原特异性抗体的产生方面，CpG-ODN增加了受IFN-γ调节的IgG2a的水平，但受IL-4调节的IgE产生受到抑制。此外，通过皮肤施用 CpG-ODN 大大减弱了经历 IgE 型免疫反应的小鼠中 IgE 的产生。通过皮肤施用 CpG-ODN 可能会将免疫反应从 Th2 转变为 Th1 样反应。这些结果表明，对于患有 AD 等疾病（以 Th2 主导的炎症为特征）的患者来说，通过皮肤施用 CpG-ODN 是一种简单的策略。 (c) 2005 Elsevier B.V 保留所有权利。
CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Co-administration of CpG-ODN and OVA to the disrupted skin elicited an antigen-specific Th1-predominant immune response and enhanced the production of Th1-type cytokines, IL-12 and IEN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. Cytokine production was supported by the expression of mRNA in the draining lymph node. In terms of antigen-specific antibody production, the level of IgG2a which is regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Furthermore, administration of CpG-ODN via the skin drastically attenuated the production of IgE in mice undergoing IgE-type immune response. Administration of CpG-ODN through the skin may shift the immune response from Th2 to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases like AD, which is characterized by Th2-dominated inflammation. (c) 2005 Elsevier B.V All rights reserved.