Molecular and Functional Analysis of NLR Family Members

NLR 家族成员的分子和功能分析

基本信息

批准号：
10409773
负责人：
Jenny P Ting
金额：
$ 50.24万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10409773
关键词：
Affect Affinity Agonist Agreement Anti-Inflammatory Agents Attenuated Autophagocytosis Bacterial Infections Binding Cell Nucleus Cells Complex DNA DNA Binding DNA receptor Data Exhibits FRAP1 gene Family Family member Foundations Gene Expression Genes Genetic Transcription Immune Immune response Immune signaling Immunity Immunologic Receptors Immunology Infection Inflammasome Inflammation Inflammatory Inflammatory Response Interferons Interleukin-1 beta Interleukin-18 Investigation Lead Leucine-Rich Repeat Licensing Ligand Binding Ligands Literature MHC Class I Genes MHC Class II Genes Mediating Mitochondria Mitochondrial Proteins Molecular Natural Immunity Nature Nucleic Acid Binding Nucleic Acids Pathway interactions Pattern Pattern recognition receptor Proteins RNA RNA Binding RNA Viruses RNA-Binding Proteins Regulation Regulatory T-Lymphocyte Role Signal Transduction Stimulator of Interferon Genes Stimulus T-Lymphocyte TBK1 gene TRAF6 gene Testing Toll-like receptors Trans-Activators Transcriptional Regulation Tretinoin Ultraviolet Rays Virus Diseases adaptive immunity cytokine experimental study immune activation innovation macrophage microbial novel pathogen promoter receptor receptor binding receptor function response sensor transcription factor viral DNA

项目摘要

Project Abstract-Revised with Changes NLRs (NOD-like receptors) are intracellular sensors, serving divergent functions in the regulation of innate immunity. While the best-studied NLRs exhibit positive function during immunity, we and others documented several NLRs that are anti-inflammatory in nature and these cause reduced inflammatory and immune activation during infection and inflammation. As examples, NLRX1 and NLRC3 serve as brakes of inflammatory response during viral and/or bacterial infection. One of the functions mediated by NLRX1 is that it reduces the RNA sensing pathway. By contrast, another inhibitory NLR, NLRC3, reduces the DNA sensing pathway mediated by STING and attenuates the proliferative pathway mediated by PI3K. Interestingly, two groups have shown that the LRR domain of NLRX1 can bind RNA, although the functional consequence of this finding is less clear. Recently, we have obtained multiple evidence that NLRC3 is an intracellular receptor for nucleic acids as well. Evidence for the direct binding of NLRs to their ligands is of paramount importance because an over-riding issue in the NLR field is whether NLRs are authentic ligand-binding receptors. The association of these NLRs with their putative nucleic acid agonists provides transformative evidence that some NLRs are indeed receptors of nucleic acids. An investigation of the interaction of NLRX1 and NLRC3 with nucleic acids, and how this interaction impacts cellular responses during microbial and non-microbial associated perturbation should be of great significance. In addition, we also find that another NLR, NLRP12, might intersect with the RNA sensing pathway. We will investigate if this is achieved through direct RNA binding or through indirect interactions with other RNA binding receptors. Finally, we find that a DNA receptor, AIM2, is highly expressed in immune cells other than macrophages. We will explore its functions in other immune cells, and propose experiments to assess if it has functions other than inflammasome activation.

随着更改的摘要浏览项目 NLR（NOD样受体）是细胞内传感器，在调节先天免疫力方面具有不同的功能。尽管最佳研究的NLR在免疫力期间表现出积极的功能，但我们和其他人记录了几种具有抗炎本质的NLR，这些NLR在感染和炎症过程中会降低炎症和免疫激活。作为示例，NLRX1和NLRC3在病毒和/或细菌感染过程中用作炎症反应的制动器。 NLRX1介导的功能之一是它降低了RNA感应途径。相比之下，另一种抑制性NLR NLRC3降低了通过刺激介导的DNA感应途径，并减轻了由PI3K介导的增殖途径。有趣的是，两组表明NLRX1的LRR结构域可以结合RNA，尽管该发现的功能后果还不太清楚。最近，我们获得了多个证据，表明NLRC3也是核酸的细胞内受体。 NLR与配体的直接结合的证据至关重要，因为NLR领域中的过度问题是NLR是否是真实的配体结合受体。这些NLR与推定的核酸激动剂的关联提供了变革性的证据，表明某些NLR确实是核酸的受体。对NLRX1和NLRC3与核酸的相互作用的研究，以及这种相互作用如何影响微生物和非微生物相关扰动期间的细胞反应。此外，我们还发现另一个NLR NLRP12可能与RNA感应途径相交。我们将研究这是通过直接RNA结合或通过与其他RNA结合受体的间接相互作用来实现的。最后，我们发现DNA受体AIM2在巨噬细胞以外的免疫细胞中高度表达。我们将探索其在其他免疫细胞中的功能，并提出实验以评估其除炎症体激活以外的功能是否具有功能。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（5）

Holding the inflammatory system in check: NLRs keep it cool.

DOI：
10.12703/p7-15
发表时间：
2015
期刊：
F1000prime reports
影响因子：
0
作者：
Jha S;Pan-Yun Ting J
通讯作者：
Pan-Yun Ting J

Gut microbiota, NLR proteins, and intestinal homeostasis.

肠道微生物群、NLR 蛋白和肠道稳态。

DOI：
10.1084/jem.20181832
发表时间：
2020-10-05
期刊：
The Journal of experimental medicine
影响因子：
0
作者：
Guo H;Gibson SA;Ting JPY
通讯作者：
Ting JPY

Human major histocompatibility complex class II-associated invariant chain gene promoter. Functional analysis and in vivo protein/DNA interactions of constitutive and IFN-gamma-induced expression.

人类主要组织相容性复合体 II 类相关的不变链基因启动子。

DOI：
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Brown,AM;Wright,KL;Ting,JP
通讯作者：
Ting,JP

Plexin-B2 and Plexin-D1 in dendritic cells: expression and IL-12/IL-23p40 production.

DOI：
10.1371/journal.pone.0043333
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Holl EK;Roney KE;Allen IC;Steinbach E;Arthur JC;Buntzman A;Plevy S;Frelinger J;Ting JP
通讯作者：
Ting JP

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury.