Fcgamma mediated regulation of dendritic cell function

描述（由申请人提供）：树突状细胞（dc）是特化的抗原呈递细胞，可以介导T细胞免疫和免疫耐受。传递给DC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)系统包括激活和抑制受体，通常在细胞表面共表达。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。我们最近发现选择性阻断抑制Fc？R, Fc ?DC上的RIIB导致DC活化并增强T细胞免疫的产生。这种DC成熟是独特的，其特征是诱导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dc具有激活人体内产生CD4和CD8 T细胞的il - 17的能力。我们的假设是Fc的平衡？R信号影响dc对Th17细胞的诱导。本应用的目的是：1)比较Fc诱导的人类产生il - 17的T细胞的特性。R激活dc，使其与炎性细胞因子酶酵素或肽聚糖一起成熟。2)评价激活Fc？Rs及下游分子在DC介导的Th17-1细胞活化中的作用3)评价DC负载活化的凋亡肿瘤细胞诱导Th17-1细胞的抗肿瘤功能。这些研究将帮助我们理解Fc？受体对树突状细胞生物学的影响，并为Fc？R介导的炎症、疾病和肿瘤免疫的免疫调节。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。我们之前已经证明dc的功能可以通过改变它们的Fc？受体。在这个应用中，我们将研究Fc？受体平衡对dc诱导Th17细胞的能力、诱导Th17细胞的途径以及dc诱导Th17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.