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

AhR 对树突状细胞的细胞功能和通讯的重要性

• 批准号: 8518324
• 负责人: CHRISTOPH F A VOGEL
• 金额: $ 33.96万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518324
• 关键词: ARNT gene; Address; Affect; Amino Acids; Aryl Hydrocarbon Receptor; Autoimmune Diseases; Biological; Biological Process; Bone Marrow; CCR6 gene; COS Cells; Cell Differentiation process; Cell Nucleus; Cell model; Cell physiology; Cells; Communication; Confocal Microscopy; Critical Pathways; Data; Deletion Mutation; Dendritic Cells; Dendritic cell activation; Development; Dioxins; Disease; Energy Transfer; Exposure to; Gene Targeting; Genetic; Goals; Health; Human; Human Cell Line; Hypersensitivity; Immune System Diseases; Immune response; Immune system; Immunity; Immunologic Deficiency Syndromes; In Vitro; Inflammatory; Inflammatory Response; Interleukin-10; Interleukin-17; Lead; Ligands; Link; Liver; Measures; Mediating; Mediator of activation protein; Modeling; Molecular; Mus; NF-kappa B; Natural Immunity; Pathway interactions; Play; Population; Predisposition; Prevention therapy; Proliferation Marker; Proteins; Receptor Activation; Receptor Signaling; Regulatory T-Lymphocyte; Role; Signal Pathway; Signal Transduction; Small Interfering RNA; Spleen; Stimulus; Surface; T cell differentiation; T-Cell Proliferation; T-Lymphocyte; T-Lymphocyte Subsets; TNFSF5 gene; Testing; Tetrachlorodibenzodioxin; Toxic Environmental Substances; Tryptophan; Work; aryl hydrocarbon receptor ligand; base; chemokine; chromatin immunoprecipitation; insight; interleukin-22; member; mouse model; new therapeutic target; novel; pollutant; transcription factor

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.

描述（由申请人提供）：本提案的总体目标是确定芳烃受体（AhR）与NF-？B信号在树突状细胞（DC）功能和分化调控中的作用。DC与T细胞的细胞通讯的改变可导致免疫性疾病，如自身免疫性疾病、变态反应和免疫缺陷。尤其是AhR与NF-？B RelB介导的对适当免疫应答至关重要的途径将是本研究的重点。DC是免疫或耐受的关键调节因子，NF-？B成员RelA和RelB对DC的发育、分化和功能至关重要。因此，AhR可能与NF-？B Rel蛋白调节DCs的功能，在特定的病理条件下，DCs通过激活NF-？B和AhR。这项研究可以提供一个明确的联系和机制之间的接触持久性有机污染物，如二恶英和二恶英类化合物激活AhR和疾病的发展基于其免疫毒性作用。这将允许更明确定义的终点来评估AhR激活化合物的作用，并且还可以提供开发新物质的机会，然后可以用于操纵免疫系统，并允许实施有效的预防措施。