Analysis and modification of Activation/migration signal of cutaneous dendritic cells and its therapeutic application

树突状细胞（DC）是一种重要的抗原提呈细胞，在各种皮肤疾病的发生和维持中起着重要作用。DC的活化和迁移被认为是由周围皮肤环境精细调节的。在1999年，我们阐明了半抗原涂敷后表皮DC的活化模式（J Invest Dermatol（Synp Proc）4：164，1999），以及TNF-α和IL-6对DC迁移到表皮中的作用（J Dermatol Sci 19：166，1999）。在2000年，我们研究了Bowen病中DC和肿瘤角质形成细胞之间的关系（Brit J Dermatol 143：1211-1216，2000）。我们还开始研究抗氧化剂调节DC功能的应用，结果表明CX-659 S通过抑制DC功能和IL-1b和TNF-α的产生来抑制半抗原诱导的接触敏感性（Int. Arch. Allergy Immunol 123：341，2000）。我们还分析了巨噬细胞对黑色素瘤细胞侵袭的作用，特别是关于细胞因子的产生（Int J Cancer 85，182，2000，Jap J Cancer Res 91：906，2000）。2001年，我们阐明了角质形成细胞产生细胞因子/趋化因子的调节系统以及IL-13受体、IFN-γ和IL-8在各种皮肤病中的定位（J Dermatol Sci 25：229-235，2001，Cytokine 13：75-84，2001，Eur J Dermatol 11：105，2001，J Dermatol Sci 26：119，2001，J Dermatol Sci，（in press），Eur J Dermatol，（in press），Dermatology，（in press））。我们还证明了DC参与肿瘤消退、肉芽肿形成和皮肤淋巴滤泡形成（Dendriti Cells 11：13，2001，Clin Exp Dermatol（出版中），Eur J Dermatol，（出版中））。

Dendritic cells (DC) are very important antigen-presenting cells in the initiation and maintenance of various skin disorders. The activation and migration of DC are thought to be finely regulated by the surrounding cutaneous milieu. In 1999, we elucidated the activation pattern of epidermal DC after hapten-painting (J Invest Dermatol (Synp Proc) 4 : 164, 1999), and the role of TNF-a and IL-6 on the immigration of DC into the epidermis (J Dermatol Sci 19 : 166, 1999). In 2000, we investigated the relationship between DC and tumor keratinocytes in Bowen's disease (Brit J Dermatol 143 : 1211-1216, 2000). We also started to examine the application of anti-oxidant to modulate the DC function, showing that the CX-659S inhibits the hapten-induced contact sensitivity by inhibiting the DC function and the production of IL-1b and TNF-a(Int. Arch. Allergy Immunol 123 : 341, 2000). We also analyzed the effects of macrophages on the invation of melanoma cells in special reference with cytokine production ( Int J Cancer 85, 182, 2000, Jap J Cancer Res 91 : 906, 2000). In 2001, we clarified the regulatory system of cyto/chemokine production of keratinocytes and the localization of IL-13 receptor, IFN-g and IL-8 in various skin diseases (J Dermatol Sci 25 : 229-235, 2001, Cytokine 13 : 75-84, 2001, Eur J Dermatol 11 : 105, 2001, J Dermatol Sci 26 : 119, 2001, J Dermatol Sci, (in press), Eur J Dermatol, (in press), Dermatology, (in press)). We also demonstrated the participation of DC in the tumor regression, granuloma formation and cutaneous lymphfollicle formation (Dendriti Cells 11 : 13, 2001, Clin Exp Dermatol (in press), Eur J Dermatol, (in press)).