转录因子IRF-5在病毒感染期间调节小鼠CD8+T细胞中的脂质代谢和线粒体功能
Linh Thuy Mai1, Sharada Swaminathan1, Trieu Hai Nguyen1
1Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, QC, Canada.
The EMBO journal
|June 10, 2025
概括
转录因子IRF-5在慢性病毒感染期间限制CD8+T细胞耗尽. 缺少IRF-5会通过破坏脂质代谢和线粒体活动来损害T细胞功能.
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:
- 在慢性感染期间,CD8+ T细胞耗尽会损害免疫反应.
- 转录因子调节T细胞耗尽,但它们在病毒感染中的作用尚未完全理解.
研究的目的:
- 调查转录因子IRF-5在慢性淋巴细胞胆膜炎病毒 (LCMV CL13) 感染期间调节CD8+T细胞耗尽中的作用.
主要方法:
- 慢性病毒感染的小鼠模型 (LCMV CL13).
- 分析CD8+T细胞种群,包括基因表达,细胞因子产生和生存率.
- 评估代谢参数,如脂质代谢,氧化应激和线粒体功能.
主要成果:
- 在CD8+T细胞中IRF-5缺乏会加剧慢性LCMV感染期间的疲劳.
- 缺乏IRF-5的T细胞显示出抑制受体和TOX的上调,细胞因子的产生减少,生存率降低.
- 缺少IRF-5会导致脂质代谢缺陷,脂质过氧化增加,线粒体ROS增强,氧化酸化减少.
结论:
- IRF-5是保护CD8+T细胞免受功能衰竭的关键调节剂.
- 在慢性病毒感染期间,IRF-5在维持T细胞代谢平衡和线粒体功能方面发挥着至关重要的作用.
相关概念视频
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
T Cell Types and Functions
959
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...
959
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K


