限制胆固醇生物合成流自发启动I型IFN信号
Autumn G York1, Kevin J Williams2, Joseph P Argus1
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|December 22, 2015
概括
I型干扰素信号改变细胞脂质代谢,增加胆固醇进口并增强病毒抵抗力. 限制胆固醇合成意外地激活了这种免疫反应,揭示了代谢与先天免疫的联系.
科学领域:
- 免疫学
- 代谢途径
- 细胞脂质代谢
背景情况:
- 通过合成和进口获得的细胞脂质对功能至关重要.
- I型干扰素 (IFN) 是关键的抗病毒细胞因子.
- 代谢重编程在免疫反应中得到越来越多的认可.
研究的目的:
- 调查I型IFN信号如何影响细胞脂质代谢.
- 确定新陈代谢在抗病毒免疫中的作用.
- 揭示脂质生物合成与先天免疫的机制.
主要方法:
- 用同位素标记分析来追踪脂质合成和进口.
- 对巨细胞的代谢途径进行基因操纵.
- 在小鼠中的病毒挑战模型.
- 对胆固醇生物合成和IFN反应的机制研究.
主要成果:
- 一种类型的IFN信号降低胆固醇和脂肪酸合成,同时增加进口.
- 基因诱导的新陈代谢变化在体内产生了对病毒的抗性.
- 降低胆固醇生物合成自发地通过STING引发I型IFN反应.
- 这种IFN反应取决于合成胆固醇水平的降低,并且可以通过胆固醇补充来逆转.
结论:
- I型IFN信号调节了有利于抗病毒防御的脂质进口的代谢转变.
- 胆固醇生物合成的干扰直接激活先天免疫,建立一个代谢-炎症循环.
- 这种代谢-炎症循环将胆固醇平衡与先天免疫反应联系在一起.
更多相关视频
相关概念视频
Cholesterol: Significance and Regulation
1.2K
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
1.2K
NF-κB-dependent Signaling Pathway
9.7K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.7K
TGF - β Signaling Pathway
10.3K
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...
10.3K
Feedback Inhibition
56.7K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
56.7K
Eukaryotic Transcription Inhibitors
10.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.8K
Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K


