Analysis of role of aryl hydrocarbon receptor for pathophysiology of atopic dermatitis

为了阐明特应性皮炎炎症反应的发生机制，本文重点研究了芳香烃受体（AhR）信号通路。在最近的研究中，Tauchi M等发现，角质形成细胞中芳香烃受体的组成性表达导致转基因小鼠的特应性皮炎样皮肤病变。他们的发现非常有趣，因为角质形成细胞分泌物导致皮肤炎症。他们的皮肤炎症就像特应性皮炎。本研究利用转基因小鼠模型和AhR过表达培养的角质形成细胞寻找AhR激活诱导的候选细胞。因此，我确定了一些促炎细胞因子的表达增加，这可能与特应性样皮炎有关。在加入AhR激活剂后，我观察到它们在培养的角质形成细胞中的表达增加。提示AhR激活可诱导角质形成细胞表达某些促炎细胞因子，树突状细胞在特应性皮炎的炎症反应中起重要作用。我推测角质形成细胞中AhR的激活诱导树突状细胞的活性。

To elucidate the mechanism how to induce inflammation in atopic dermatitis, I focused aryl hydrocarbon receptor (AhR) signaling pathway. In the recent study, Tauchi M et al. showed that constitutive expression of aryl hydrocarbon receptor in keratinocytes causes atopic dermatitis-like skin lesions in transgenic mouse.Their discovery is very intriguing because secretion production by keratinocyte cause skin inflammation. And their skin inflammation is like atopic dermatitis. I seeked candidates which are induced under AhR activation by using previous transgenic mouse model and AhR-overexpressed cultured keratinocyte. So I identified increasing expression of some proinflammatory cytokines, which may be related in atopic-like dermatitis. I observed increase expression of them in culutured keratinocyte after the addition of AhR activator. These data suggest that AhR activation induced expression of some proinflammatory cytokines in keratinocyte.In atopic dermatitis, dendritic cell has a significant role in establishment of inflamation. I speculate that AhR activation in keratinocyte induce dendritic cell activity.