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Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis¹

School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by Grant-in-aid 14657594 for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to Y.A.).

² Address correspondence and reprint requests to Dr. Yukihiko Aramaki, School of Pharmacy, Tokyo University of Pharmacy and Life Science 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. E-mail address: aramaki{at}ps.toyaku.ac.jp

³ Abbreviations used in this paper: ODN, oligodeoxynucleotide; AD, atopic dermatitis; Treg, regulatory T cell; LN, lymph node.

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