MyD88蛋白质不稳定减轻了NF-κB依赖于对巨细胞亡的保护
Duško Lainšček1,2,3, Simon Horvat4, Klemen Dolinar5
1Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Cell communication and signaling : CCS
|November 16, 2024
概括
一个MyD88突变破坏了炎症体调节,导致巨细胞中氧化应激增加和亡. 这突出了MyD8888的亮点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 信号通路对于先天免疫和细胞平衡至关重要.
- MyD88是先天免疫信号传递中的关键适应蛋白.
- 这些通路的失调会导致疾病.
研究的目的:
- 研究MyD88特定突变 (D162E) 在炎症酶调节和细胞平衡中的作用.
- 了解这种突变对免疫细胞功能和亡的影响.
- 探索MyD88相关疾病的潜在治疗策略.
主要方法:
- 在小鼠中引入MyD88 (MyD88D162E) 中的caspase-1识别位突变.
- 在突变和野生型小鼠中使用DSS诱导大肠炎.
- 分析细胞因子表达,氧化应激,线粒体功能和骨髓衍生巨细胞 (BMDMs) 中的亡.
- 评估脂多糖 (LPS) 和易布鲁替尼治疗对细胞表型的影响.
主要成果:
- MyD88D162E突变取消了炎症酶依赖的负调节.
- 突变小鼠显示结肠炎症减少,但在BMDM中细胞因子表达没有变化.
- MyD88D162E BMDMs 呈现出增加的氧化应激,线粒体功能障碍和亡易感性.
- 通过LPS激活NF-κB可以减轻亲细胞亡的表型.
结论:
- MyD88wt信号传递对于NF-κB激活和保护巨细胞免受亡至关重要.
- MyD88D162E突变通过增加细胞亡来损害细胞平衡.
- 调节MyD88蛋白水平,而不仅仅是信号,可能为MyD88驱动的淋巴瘤提供治疗方法.
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 Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
The JAK-STAT Signaling Pathway
8.7K
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...
8.7K
Phagocytosis of Apoptotic Cells
3.7K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
3.7K


