通过AGR2介导的细胞间通信,通过促进TRAF3的醇氧化来控制抗病毒免疫反应
Mengqi Jia1, Xiaojing Chen1, Wenxue Guo1
1Key Laboratory of Experimental Teratology of Ministry of Education, Institute of Medical Sciences, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Redox biology
|March 14, 2025
概括
前梯度2 (AGR2),一种蛋白质二硫化异酶,通过抑制I型干扰素的产生来抑制抗病毒免疫力. AGR2的目标是TRAF3,一个关键的免疫信号蛋白,以维持免疫平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 蛋白质二硫化异构酶 (PDIs) 对于蛋白质的折叠和功能至关重要.
- 除了二硫化物键催化之外,PDI还有不同的作用,包括在病理生理条件下.
- 前侧梯度2 (AGR2) 是一种PDI成员,在免疫力方面具有很大程度上尚未探索的功能.
研究的目的:
- 为了研究AGR2在抗病毒免疫力中的作用.
- 阐明AGR2调节免疫反应的分子机制.
- 确定增强抗病毒免疫力的潜在治疗点.
主要方法:
- 在RNA病毒感染后在上皮细胞中对AGR2表达的分析.
- 在体外和体内研究评估AGR2对I型干扰素 (IFN-I) 生产的影响.
- 通过内细胞化对免疫细胞 (巨细胞) 通过内细胞化对AGR2内部化的研究.
- 共同免疫沉和质谱测量以确定AGR2结合伙伴.
- 生物化学试验分析TRAF3无化和与TBK1.1的复合形成.
主要成果:
- RNA病毒感染上调了上皮细胞中的AGR2表达和分泌.
- 细胞内和细胞外的AGR2都抑制了IFN-I的产生.
- 分泌的AGR2被巨细胞内部化,抑制了它们的免疫反应.
- AGR2与TRAF3形成二硫化键,抑制TRAF3的泛化和TBK1复合体的形成.
- 在Cys296的TRAF3突变减少了AGR2的修饰,增强了TRAF3的自我结合,并促进了IFN-I的产生.
结论:
- AGR2作为抗病毒免疫的负调节剂.
- AGR2通过氧化修饰TRAF3来抑制IFN-I的产生,从而损害其信号传输.
- 这种由AGR2对TRAF3的依赖氨酸的修饰对于先天性免疫恒常性至关重要.
相关概念视频
Immune Response Against Viral Pathogens
722
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
722
T Cell Types and Functions
740
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
740
Cytotoxic T Cells-mediated Immune Response
823
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
823
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
T Cell Activation and Clonal Selection
620
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
620


