Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis
Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis
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DOI：
10.4049/jimmunol.178.1.584
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Aramaki, Yukihiko
中科院分区：
文献类型：
--
作者：
Inoue, Joe;Aramaki, Yukihiko
特应性皮炎（AD）是一种以血浆总IgE水平升高、肥大细胞和嗜酸性粒细胞浸润以及Th 2细胞表达细胞因子为特征的皮炎性炎症性皮肤病。已知保持在常规条件下的NC/Nga小鼠会出现类似于人AD的皮肤病变。在这项研究中，我们研究了在NC/Nga小鼠保持在常规条件下，经皮应用CpG-寡脱氧核苷酸（ODN），这起着至关重要的作用，通过增强Th 1型和抑制Th 2型反应的免疫应答的改变。从细胞因子mRNA和抗体水平来看，CpG-ODN显著改变了Th 2型向Th 1型的免疫应答。血清IgE水平降低，IgG 2a表达上调。将CpG-ODN应用于皮肤也减少肥大细胞的炎性浸润，并且观察到皮肤病变中的抑制。此外，在用CpG-ODN处理的皮肤中观察到调节性T细胞（其被认为是免疫抑制性T细胞）的产生。这些结果表明CpG-ODN对以Th 2为主的炎症反应为特征的AD患者的免疫治疗是有效的。
Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN remarkably changed the immune response from type Th2 to Th1 as determined from cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased inflammatory infiltration of mast cells, and suppression in the skin lesions was observed. Furthermore, the generation of regulatory T cells, which are considered immune suppressive T cells, was observed in the skin on treatment with CpG-ODN. These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation.