一个病态的关节-肝脏轴,由由母蛋白激活的CD4+ T细胞介导
Junzhi Yi1,2, Hui Zhang1,2,3, Fangyuan Bao1,2
1Department of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Signal transduction and targeted therapy
|May 7, 2024
概括
关节出血 (动脉瘤) 会损害软骨,激活 CD4+ T 细胞,从而损害肝功能. 在软骨中恢复Akt路径可以防止这种关节肝轴损伤.
科学领域:
- 免疫学 免疫学 免疫学
- 整形外科 整形外科 整形外科
- 肝病学 肝病学是一种肝病学.
背景情况:
- 膝关节传统上被视为一个封闭的系统,对关节疾病如何影响远处器官的研究有限.
- 关节疾病,特别是关节炎,对偏远器官的病理影响仍未得到充分研究.
研究的目的:
- 为了研究关节损伤,特别是血关节炎和远端器官功能障碍之间的病理关系,专注于肝脏.
- 为了阐明细胞和分子机制背后的关节-肝脏轴在血关节炎.
- 为了识别潜在的治疗点为血关节炎诱导的器官损伤.
主要方法:
- 对患有创伤后关节损伤和血关节的患者的临床数据分析.
- 建立一个小鼠模型用于动脉硬化,以研究软骨退化和肝损伤.
- 流细胞计和细胞枯竭实验,以分析CD4+T细胞参与.
- 对CD4+T细胞的II型原蛋白 (COL II) 激活的分析.
- 大量RNA测序和单细胞qPCR用于研究软骨中的Akt路径.
- 在小鼠和猪模型中使用Akt激活剂和抑制剂的体内实验.
主要成果:
- 血关节炎与临床数据中肝功能恶化有关,并诱导了小鼠的软骨退行和肝损伤.
- 血关节炎促进了CD4+ T细胞分化为Th17细胞,CD4+ T细胞枯竭逆转了肝损伤.
- 退化的软骨释放了COL II,激活了CD4+T细胞,而软骨Akt通路则被血液抑制.
- 在老鼠和猪模型中,关节内Akt激活可以防止软骨退化和随后的肝功能障碍.
结论:
- 发现了一种新的病理性关节 - 肝轴,由母蛋白激活的CD4+T细胞介导.
- 血关节炎通过抑制Akt路径诱导软骨降解,释放激活CD4+T细胞的COL II,从而导致肝损伤.
- 向软骨中的Akt通路为与血液结相关的肝病提供了潜在的治疗策略.
更多相关视频
11:36Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
3.0K
12:23Flow Cytometry Analysis of Immune Cell Subsets within the Murine Spleen, Bone Marrow, Lymph Nodes and Synovial Tissue in an Osteoarthritis Model
Published on: April 24, 2020
19.6K
相关概念视频
01:24T Cell Types and Functions
1.0K
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...
1.0K
01:20The JAK-STAT Signaling Pathway
8.8K
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...
8.8K
01:24Liver Regeneration
3.3K
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...
3.3K