Recognition and Signaling Via TLR13

通过 TLR13 进行识别和发出信号

• 批准号: 7474605
• 负责人: Dekai Zhang
• 金额: $ 24.98万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474605
• 关键词: Antibodies; Biological; Biology; Cells; Detection; Double-Stranded RNA; Family; Host Defense; Immune response; Immune system; Inflammatory; Interferons; Knockout Mice; Mediator of activation protein; Molecular; Natural Immunity; Pathway interactions; Pattern; Phase; Play; RNA; Role; Signal Pathway; Signal Transduction; Testing; Toll-like receptors; Viral; Virus Diseases; cytokine; defense response; genome database; intracellular protein transport; member; microorganism; novel; pathogen; protein localization location; receptor; sensor

DESCRIPTION (provided by applicant): Toll-like receptors (TLRs), the key molecular sensors used by the mammalian innate immune system to detect microorganisms, were identified only in the late 1990s. These evolutionarily conserved receptors recognize pathogen associate molecular patterns, and their activation leads to an appropriate host-defense response. Tremendous progress has been made over the past few years in determining the role of TLRs in innate immunity. However we are still in an exponential phase of discovery about many important aspects of TLR biology. We have recently cloned a novel member of the mammalian Toll-like receptor (TLR) family, TLR13. TLR13 appears to activate only the MyD88-independent TRIF pathway, inducing type 1 interferon and inflammatory cytokines. Remarkably, TLR 13 seems able to recognize a viral molecular pattern, double-stranded RNA (dsRNA). We therefore hypothesize that TLR13 represents a novel member of the TLR family that plays a role in the recognition of dsRNA during viral infection to activate innate immune response. We will generate specific antibodies against TLR13 to determine the endogenous protein localization. We will study the pattern of expression of TLR13 and determine whether its cellular localization and level of expression are altered upon stimulation of cells with viral dsRNA as well as other inflammatory mediators. Then we will determine whether it cooperates with other members of the TLR family. Furthermore we will clarify and determine the signaling pathways activated by TLR13. Finally we will generate a TLR13 knock-out mouse to systematically analyze the biological role of TLR13.

描述（由申请人提供）：Toll 样受体 (TLR) 是哺乳动物先天免疫系统用来检测微生物的关键分子传感器，直到 20 世纪 90 年代末才被鉴定。这些进化上保守的受体识别病原体相关分子模式，它们的激活导致适当的宿主防御反应。过去几年，在确定 TLR 在先天免疫中的作用方面取得了巨大进展。然而，对于 TLR 生物学的许多重要方面，我们仍处于发现的指数阶段。我们最近克隆了哺乳动物 Toll 样受体 (TLR) 家族的一个新成员，TLR13。 TLR13 似乎仅激活 MyD88 独立的 TRIF 通路，诱导 1 型干扰素和炎症细胞因子。值得注意的是，TLR 13 似乎能够识别病毒分子模式，即双链 RNA (dsRNA)。因此，我们假设 TLR13 代表 TLR 家族的新成员，在病毒感染期间识别 dsRNA 中发挥作用，从而激活先天免疫反应。我们将生成针对 TLR13 的特异性抗体来确定内源蛋白的定位。我们将研究 TLR13 的表达模式，并确定其细胞定位和表达水平是否在病毒 dsRNA 以及其他炎症介质刺激细胞后发生改变。然后我们将确定它是否与TLR家族的其他成员合作。此外，我们将阐明并确定 TLR13 激活的信号通路。最后我们将构建TLR13敲除小鼠来系统分析TLR13的生物学作用。

项目成果

Transcriptional regulation of Tlr11 gene expression in epithelial cells.

上皮细胞中 Tlr11 基因表达的转录调控。

• 发表时间: 2009-11-27
• 作者: Cai, Zhenyu;Shi, Zhongcheng;Sanchez, Amir;Zhang, Tingting;Liu, Mingyao;Yang, Jianghua;Wang, Fen;Zhang, Dekai
• 通讯作者: Zhang, Dekai

Transcriptional regulation of the novel Toll-like receptor Tlr13.

新型 Toll 样受体 Tlr13 的转录调控。

• 发表时间: 2009-07-31
• 作者: Shi, Zhongcheng;Cai, Zhenyu;Wen, Shu;Chen, Caoyi;Gendron, Christi;Sanchez, Amir;Patterson, Kevin;Fu, Songbin;Yang, Jianhua;Wildman, Derek;Finnell, Richard H;Zhang, Dekai
• 通讯作者: Zhang, Dekai

Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13.

Toll 样受体 13 特异性识别单链 RNA 的结构基础。

• 发表时间: 2015-10
• 影响因子: 16.8
• 作者: Song, Wen;Wang, Jia;Han, Zhifu;Zhang, Yifan;Zhang, Heqiao;Wang, Weiguang;Chang, Junbiao;Xia, Bingshu;Fan, Shilong;Zhang, Dekai;Wang, Jiawei;Wang, Hong;Chai, Jijie
• 通讯作者: Chai, Jijie