Inoue Joe, Yotsumoto Satoshi, Sakamoto Takatoshi, Tsuchiya Seishi, Aramaki Yukihiko
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan,
Pharm Res. 2005 Oct;22(10):1627-33. doi: 10.1007/s11095-005-6834-7. Epub 2005 Sep 26.
CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and the suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to a tape-stripped skin of NC/Nga mouse, a human atopic dermatitis (AD) model, by evaluating the production of cytokines and immunoglobulin isotypes.
Model antigen, ovalbumin (OVA), and CpG-ODN were applied on to the shaved skin. The penetration of OVA and CpG-ODN was evaluated using confocal laser scanning microscopy (CLSM). Secretion of cytokine from splenocytes and changes in immunoglobulin isotype levels were determined by enzyme-linked immunosorbent assay (ELISA).
Through CLSM it was revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Coadministration of CpG-ODN and OVA to the skin elicited an antigen-specific, Th1-predominant immune response and enhanced the production of IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. In terms of antigen-specific antibody production, the level of IgG2a regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed.
Administration of CpG-ODN with antigen through the skin may shift the immune response from a Th2- to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases such as AD, which is characterized by Th2-dominated inflammation.
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免疫球蛋白亚型的产生,研究了CpG-ODN对应用于NC/Nga小鼠(一种人类特应性皮炎(AD)模型)胶带剥离皮肤的抗原免疫反应的影响。
将模型抗原卵清蛋白(OVA)和CpG-ODN应用于剃毛后的皮肤。使用共聚焦激光扫描显微镜(CLSM)评估OVA和CpG-ODN的渗透情况。通过酶联免疫吸附测定(ELISA)测定脾细胞中细胞因子的分泌以及免疫球蛋白亚型水平的变化。
通过CLSM发现,模型抗原OVA和CpG-ODN很容易穿透胶带剥离的皮肤。将CpG-ODN与OVA共同应用于皮肤引发了抗原特异性的、以Th1为主的免疫反应,并增强了IFN-γ的产生。另一方面,Th2型细胞因子IL-4的产生被显著抑制。在抗原特异性抗体产生方面,由IFN-γ调节的IgG2a水平因CpG-ODN而升高,但由IL-4调节的IgE产生受到抑制。
通过皮肤将CpG-ODN与抗原一起给药可能会使免疫反应从Th2样反应转变为Th1样反应。这些结果表明,对于以Th2主导炎症为特征的AD等疾病患者,经皮肤给予CpG-ODN是一种简单的策略。