Receptors Of Plasmacytoid Dendritic Cells And Their Ligands

浆细胞样树突状细胞受体及其配体

基本信息

批准号：
8118115
负责人：
Wei Cao
金额：
$ 37.02万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2013-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Plasmacytoid dendritic cells (pDCs) represent a specialized immune cell population that produces large amounts of type I interferons (IFN) in response to viruses and function as a critical linkage between innate and adaptive immunity. Our long-term goal is to study the functions of pDCs pertaining to specific physiological environments or conditions. The central hypothesis is that unique pDC receptors play key roles in the biological functions of pDCs through interactions with their ligands and activating specific intracellular pathways. We based that hypothesis on the observation that 1) human pDC receptor ILT7 activates an ITAM-mediated signaling pathway to inhibit IFN responses by pDCs, 2) the potential ligand of ILT7 is expressed by a group of human breast cancer cell lines, and 3) human pDC receptor BDCA2, a C-type lectin with unknown ligand, potentially utilizes the ITAM-mediated mechanism to regulate pDCs' IFN responses. The specific aims are to: 1) Determine the detailed signaling mechanism of ILT7 in human pDCs and study the underlining mechanism how ITAM-mediated pathway intersects with the Toll-like receptor (TLR)-mediated innate immune responses. 2) Identify the natural ligand of ILT7, which is expressed by human breast cancer cell lines, and study its tissue expression in relation with pDC infiltration. The function of the ligand on pDCs through interaction with ILT7 will be thoroughly elucidated. 3) Determine the detailed signaling mechanism used by BDCA2. The natural ligand for BDCA2 is to be screened using a reporter cell system capable of sensing surface BDCA2 engagement. A wide range of carbohydrate structures, microbial agents and cell-associated factors will be tested in this aim. The altered presence and functions of pDCs have been implicated in human ailments such as autoimmune diseases, infectious diseases and cancer. By focusing on the two surface receptors uniquely expressed by human pDCs through pursuing their ligands and shared intracellular signaling mechanism, the proposed studies will greatly advance research on the physiological functions of pDCs and may generate direct molecular targets with therapeutic potential.

描述（由申请人提供）：浆细胞样树突状细胞（pDC）代表一种特殊的免疫细胞群，可产生大量 I 型干扰素（IFN）以响应病毒，并作为先天免疫和适应性免疫之间的关键联系。我们的长期目标是研究 pDC 在特定生理环境或条件下的功能。核心假设是，独特的 pDC 受体通过与其配体相互作用并激活特定的细胞内途径，在 pDC 的生物学功能中发挥关键作用。我们的假设基于以下观察：1) 人类 pDC 受体 ILT7 激活 ITAM 介导的信号通路以抑制 pDC 的 IFN 反应，2) ILT7 的潜在配体由一组人类乳腺癌细胞系表达，3)人 pDC 受体 BDCA2 是一种配体未知的 C 型凝集素，可能利用 ITAM 介导的机制来调节 pDC 的 IFN 反应。具体目标是： 1) 确定人类 pDC 中 ILT7 的详细信号传导机制，并研究 ITAM 介导的通路与 Toll 样受体 (TLR) 介导的先天免疫反应交叉的基本机制。 2) 鉴定人乳腺癌细胞系表达的ILT7天然配体，并研究其组织表达与pDC浸润的关系。配体通过与 ILT7 相互作用在 pDC 上的功能将得到彻底阐明。 3) 确定BDCA2使用的详细信号机制。 BDCA2 的天然配体将使用能够感知表面 BDCA2 接合的报告细胞系统进行筛选。为此目的，将测试多种碳水化合物结构、微生物制剂和细胞相关因子。 pDC 的存在和功能的改变与自身免疫性疾病、传染病和癌症等人类疾病有关。通过关注人类pDCs独特表达的两种表面受体，通过寻找它们的配体和共享的细胞内信号传导机制，所提出的研究将极大地推进pDCs生理功能的研究，并可能产生具有治疗潜力的直接分子靶点。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL).

人浆细胞样前树突状细胞通过糖皮质激素诱导的肿瘤坏死因子受体配体 (GITRL) 激活 NK 细胞。

DOI：
10.1182/blood-2005-08-3419
发表时间：
2006-05-01
期刊：
Blood
影响因子：
20.3
作者：
S. Hanabuchi;N. Watanabe;Yi;Yu Wang;Tomoki Ito;J. Shaw;W. Cao;F. X. Qin;Yong‐jun Liu
通讯作者：
Yong‐jun Liu

Innate immune functions of plasmacytoid dendritic cells.

浆细胞样树突状细胞的先天免疫功能。