I型IFN受体阻塞通过巨细胞衍生的STAT3信号传递来缓解肝纤维化
Soo-Jeung Park1, Josefina Garcia Diaz1,2, Tina Comlekoglu1
1Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, United States.
Frontiers in immunology
|April 22, 2025
概括
阻断I型干扰素与IFNAR-1抗体的信号传递,可以减少肝脏巨细胞并缓解肝纤维化. 这种方法调节巨细胞的炎症反应,提供潜在的抗纤维性疗法.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 纤维化研究 纤维化研究
背景情况:
- 肝脏巨细胞通过炎症信号传递与肝纤维化进展有关.
- 巨细胞导致肝纤维化的确切机制尚不完全理解.
研究的目的:
- 调查I型干扰素信号传递在肝纤维化进展中的作用.
- 为了确定阻断I型干扰素信号传递对肝脏巨细胞和纤维化的影响.
主要方法:
- 使用CCl4诱导的肝纤维化小鼠模型.
- 使用IFNAR-1抗体阻止I型干扰素信号传递.
- 进行免疫细胞组成分析和基因表达造型,包括单细胞RNA-seq.
主要成果:
- CCl4治疗增加了肝脏巨细胞,特别是单细胞衍生的巨细胞,并增加了I型干扰素特征基因表达.
- 阻断IFNAR-1减少了巨细胞的透,缓解了肝纤维化,并促进了肝细胞的增殖.
- IFNAR-1阻塞改变了巨细胞中的P-STAT3/P-STAT1比率,与M2分化相关,并影响了炎症途径.
结论:
- I型干扰素信号阻断通过调节巨细胞炎症反应来缓解肝纤维化.
- 阻断IFNAR-1对开发针对I型干扰素通路的新型抗纤维性疗法充满希望.
更多相关视频
10:00High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
13.3K
06:29Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
2.1K
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
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...
7.2K
The JAK-STAT Signaling Pathway
8.4K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.4K
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
Liver Regeneration
3.2K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.2K
