Fcgamma mediated regulation of dendritic cell function

Fcγ介导的树突状细胞功能调节

• 批准号: 7905115
• 负责人: Kavita Madhav Dhodapkar
• 金额: $ 40.96万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7905115
• 关键词: Antigen-Antibody Complex; Antigen-Presenting Cells; Apoptotic; Autoimmunity; B-Lymphocytes; Beds; CD8B1 gene; Caspase-1; Cell Maturation; Cell physiology; Cell surface; Cells; Cellular biology; Data; Dendritic Cells; Dendritic cell activation; Disease; Environment; Equilibrium; Fc Receptor; Generations; Genes; Health; Human; IL17 gene; Immune; Immune Tolerance; Immunity; Immunologic Surveillance; Immunotherapy; Inflammation; Inflammatory; Interferon Type I; Interleukin-10; Link; Mediating; Monoclonal Antibodies; Multiple Myeloma; Mus; Nature; Necrosis; Outcome; Pathway interactions; Patients; Peptidoglycan; Process; Property; Protein Tyrosine Kinase; Receptor Signaling; Regulation; Role; STAT protein; Signal Transduction; Stimulus; System; T cell response; T-Cell Activation; T-Lymphocyte; Testing; Tumor Antibodies; Tumor Burden; Tumor Immunity; Zymosan; chemokine; chemokine receptor; cytokine; effective therapy; granzyme B; improved; insight; killer T cell; killings; neoplastic cell; novel; perforin; public health relevance; receptor; response; tumor; uptake

DESCRIPTION (provided by applicant): Dendritic cells (DCs) are specialized antigen presenting cells that can mediate both T cell immunity as well as immune tolerance. The nature of specific maturation signal delivered to DCs is an important determinant of DC function. Fc? receptor (Fc?R) system includes activating as well as inhibitory receptors that are usually co-expressed on the cell surface. The balance between the activating and inhibitory signals determines the outcome of immune complex mediated inflammation and immunity. We have recently shown that selective blockade of the inhibitory Fc?R, Fc?RIIB on DCs leads to DC activation and enhanced generation of T cell immunity. This DC maturation is distinct and characterized by induction of several chemokines and cytokines as well as type I interferon (IFN) response genes. Our preliminary data suggests that Fc?R matured DCs have the ability to activate IL17 producing CD4 as well as CD8 T cells in humans. Our hypothesis is that the balance of Fc?R signaling impacts induction of Th17 cells by DCs. The aims of this application are I) To compare the properties of human IL17 producing T cells induced by Fc?R activated DCs with those generated by DCs matured with inflammatory cytokines zymosan or peptidoglycan. 2) To evaluate the role of activating Fc?Rs and downstream molecules in DC mediated activation of Th17-1 cells 3) To evaluate the anti-tumor function of the Th17-1 cells induced by DCs loaded with opsonized apoptotic tumor cells. These studies will help us understand the role Fc? receptors on dendritic cell biology and provide novel insights into Fc?R mediated immune regulation in inflammation and disease as well as tumor immunity. . PUBLIC HEALTH RELEVANCE: Dendritic cells (DCs) are specialized antigen presenting cells that mediate activation of T cells. We have previously shown that the function of DCs can be modulated by altering the signaling via their Fc? receptors. In this application we will examine the effect of the modulation of the Fc? receptor balance on the ability of DCs to induce Th17 cells, the pathways involved in the induction of Th17 cells as well as the function of the Th17 cells induced by the DCs.

描述（由申请人提供）：树突状细胞（DC）是可以介导T细胞免疫和免疫耐受性的专门抗原呈递细胞。传递到DCS的特定成熟信号的性质是DC功能的重要决定因素。 FC？受体（FC？r）系统包括通常在细胞表面共表达的激活以及抑制受体。激活信号和抑制信号之间的平衡决定了免疫复合物介导的炎症和免疫力的结果。我们最近表明，DCS上的抑制性FC？r，Fc？riIB的选择性阻断导致DC激活和增强T细胞免疫的产生。该直流成熟是不同的，其特征是诱导了几种趋化因子和细胞因子以及I型干扰素（IFN）反应基因。我们的初步数据表明，FC？R成熟的DC具有激活人类中产生CD4以及CD8 T细胞的IL17的能力。我们的假设是FC信号传导的平衡会影响DC诱导Th17细胞的诱导。该应用的目的是i）比较FC激活的DC诱导的人IL17的性质与由DC生成的DC诱导的T细胞的特性，而DCS生成的DC则用炎性细胞因子Zymosan或peptidogoglycan成熟。 2）评估激活Fc？rs和下游分子在DC介导的Th17-1细胞激活中的作用3）评估由装有打印化的凋亡肿瘤细胞的DC诱导的Th17-1细胞的抗肿瘤功能。这些研究将帮助我们了解FC的角色？树突状细胞生物学的受体，并提供了FC介导的炎症和疾病免疫调节以及肿瘤免疫的新见解。 。公共卫生相关性：树突状细胞（DC）是介导T细胞激活的专门抗原呈现细胞。我们先前已经表明，可以通过通过其FC更改信号来调制DC的功能？受体。在此应用程序中，我们将检查FC调制的效果？受体平衡DC诱导Th17细胞的能力，涉及Th17细胞的途径以及由DC诱导的Th17细胞的功能。