Fcgamma mediated regulation of dendritic cell function

描述（由申请人提供）：树突状细胞（DC）是能够介导T细胞免疫以及免疫耐受的特化抗原呈递细胞。递送至DC的特异性成熟信号的性质是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上共表达的活化性以及抑制性受体。激活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的结果。我们最近表明，选择性封锁的抑制性Fc？R、FC？DC上的RIIB导致DC活化和增强的T细胞免疫的产生。这种DC成熟是独特的，其特征在于诱导几种趋化因子和细胞因子以及I型干扰素（IFN）应答基因。我们的初步数据表明，Fc？R成熟的DC具有激活人中产生IL 17的CD 4以及CD 8 T细胞的能力。我们的假设是，平衡的Fc？R信号传导影响DC诱导的Th 17细胞。本申请的目的是I）比较Fc诱导的人IL 17产生T细胞的性质？R激活的DC与由用炎性细胞因子酵母聚糖或肽聚糖成熟的DC产生的DC。2)评价活化Fc？Rs及其下游分子在DC介导的Th 17 -1细胞活化中的作用3）研究经调理的凋亡肿瘤细胞负载的DC诱导的Th 17 -1细胞的抗肿瘤作用。这些研究将有助于我们了解的作用Fc？受体的树突状细胞生物学，并提供新的见解Fc？R在炎症和疾病以及肿瘤免疫中介导的免疫调节。.公共卫生相关性：树突状细胞（DC）是介导T细胞活化的特化抗原呈递细胞。我们以前已经表明，DC的功能可以通过改变其Fc？受体。在此应用程序中，我们将研究的Fc？受体平衡对DC诱导Th 17细胞的能力、参与诱导Th 17细胞的途径以及DC诱导的Th 17细胞的功能的影响。

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.