Effect of dendritic cells treated with CpG ODN on atopic dermatitis of Nc/Nga mice.

Sang-Tae Park, Kyoung-Eun Kim, Kwangmin Na, Younghwa Kim, Tae-Yoon Kim
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引用次数: 7

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease and the pathogenesis of AD is associated with the release of various cytokines/chemokines due to activated Th(2) immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide in the context of particular base sequence (CpG motifs) are known to have the immunostimulatory activities in mice and to convert from Th(2) to Th(1) immune responses in AD. We aimed to investigate that CpG ODN, especially phosphodiester form, can stimulate the protective immunity in NC/Nga mice with AD. We isolated BMDCs from NC/Nga mice and then, cultured with GM-CSF and IL-4 for 6 days, and treated for 2 days by either phosphorothioate ODN or phosphodiester ODN. CpG ODN-treated DCs resulted in more production of IL-12. When CpG ODN-treated DCs were intravenously injected into the NC/Nga mice, the NC/Nga mice with CpG ODN-treated DCs showed significant improvement of AD symptoms and decrease of IgE level. Histopathologically, the NC/Nga mice skin with CpG ODN-treated DCs showed the decreased IL-4 and TARC expression comparing with non-injected mice. These results may suggest that phosphodiester CpG ODN-treated DCs might function as a potent adjuvant for AD in a mouse model.

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CpG ODN处理树突状细胞对Nc/Nga小鼠特应性皮炎的影响。
特应性皮炎(AD)是一种慢性炎症性皮肤病,其发病机制与激活Th(2)免疫反应导致多种细胞因子/趋化因子的释放有关。在特定碱基序列(CpG基序)的背景下,含有未甲基化CpG二核苷酸的合成寡脱氧核苷酸(ODNs)已知在小鼠中具有免疫刺激活性,并在AD中从Th(2)转化为Th(1)免疫反应。我们的目的是研究CpG ODN,特别是磷酸二酯形式,是否能刺激NC/Nga AD小鼠的保护性免疫。我们从NC/Nga小鼠中分离BMDCs,然后用GM-CSF和IL-4培养6天,再用硫代磷酸酯或磷酸二酯ODN处理2天。CpG odn处理的dc产生更多的IL-12。将CpG odn处理的dc静脉注射到NC/Nga小鼠体内,CpG odn处理的NC/Nga小鼠AD症状明显改善,IgE水平明显降低。组织病理学上,与未注射CpG odn的小鼠相比,CpG odn处理dc的NC/Nga小鼠皮肤IL-4和TARC表达降低。这些结果可能表明磷酸二酯CpG odn处理的dc可能在小鼠模型中作为AD的有效佐剂。
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