Importance of AhR for the cellular function and communication of dendritic cells

描述(由申请人提供)：本提案的总体目标是确定与核因子-βB信号相互作用的芳烃受体(AhR)在控制树突状细胞(DC)功能和分化中的调节作用。树突状细胞与T细胞细胞通讯的改变可导致自身免疫性疾病、过敏和免疫缺陷等免疫疾病。尤其是AhR与NF-BRelB介导的对适当的免疫应答至关重要的通路的相互作用将是本研究的重点。DC是免疫或耐受的关键调节因子，而核因子？B成员RelA和RelB对DC的发育、分化和功能起关键作用。因此，AhR可能与核因子？B受体蛋白相互作用，调节树突状细胞的功能，在特定的病理条件下，通过激活核因子？b和AhR来影响T细胞的分化。本研究可根据二恶英及其类似物的免疫毒性作用，为机体暴露于二恶英及其类似物等持久性有机污染物激活AhR与疾病的发生之间提供明确的联系和机制。这将允许更明确定义的终点来评估AhR激活化合物的影响，还可能提供机会开发新的物质，然后可用于操纵免疫系统，并允许实施有效的预防措施。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to identify the regulatory role of the aryl hydrocarbon receptor (AhR) interacting with NF-?B signaling in controlling function and differentiation of dendritic cells (DC). Alteration of cellular communication of DC with T cells can lead to immunological disorders like autoimmune diseases, allergy and immunodeficiency. Especially interaction of the AhR with NF-?B RelB mediated pathways critical for appropriate immune responses will be the focus of this study. DCs are key regulator of immunity or tolerance, and the NF-?B members RelA and RelB are critical for the development, differentiation and function of DC. Therefore, the AhR may interact with NF-?B Rel proteins to regulate the function of DCs, which affects T cell differentiation in particular pathological conditions mediated by activation of NF-?B and AhR. This study can provide a definite link and mechanism between the exposure to persistent organic pollutants like dioxin and dioxin-like compounds activating the AhR and the development of diseases based on their immunotoxic effects. This will allow for more clearly defined endpoints to assess the effects of AhR activating compounds and may also provide opportunities to develop new substances that can then be used to manipulate the immune system and allow for effective preventative measures to be implemented.