在早期的MASLD中,巨细胞Notch1信号通过TGFB轴调节调节性T细胞
Mengya Zhang1, Kun Li2, Xiaoxing Huang3
1Department of Pharmacology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China.
JHEP reports : innovation in hepatology
|December 24, 2024
概括
调节性T细胞 (Tregs) 在早期代谢功能障碍相关的脂肪性肝病 (MASLD) 中减少. 通过外体miR-142a-3p的巨细胞Notch1信号,损害了Treg分化,导致MASLD的进展.
科学领域:
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
背景情况:
- 肝脏免疫失衡驱动了与代谢功能障碍相关的脂肪性肝病 (MASLD).
- 调控性T细胞 (Tregs) 在早期MASLD中的确切作用以及影响其频率的机制仍然不清楚.
研究的目的:
- 研究肝脏Tregs在早期MASLD中的作用.
- 阐明巨细胞Notch1信号对Treg频率的影响.
- 确定调节MASLD中的Treg分化的分子机制.
主要方法:
- 利用高脂肪饮食小鼠模型用于早期脂肪和患者肝脏样本.
- 雇佣了巨细胞特异性的Notch1-knockout (Notch1M-KO) 的小鼠.
- 分析了外体miRNA测序,以确定影响Treg分化的miRNA.
主要成果:
- 降低的Tregs与高脂肪饮食诱导的肝肥和胰岛素抵抗相关.
- 巨细胞Notch1激活与Treg频率相反相关.
- 巨细胞中的Notch1缺乏减少了肝脂积累和增加了Treg水平.
- 巨细胞Notch1信号增加了外体miR-142a-3p,它向T细胞上的TGFBR1,损害了Treg分化.
结论:
- 肝脏Tregs在早期的MASLD中至关重要.
- 通过外体miR-142a-3p和TGFBR1的巨细胞Notch1信号传递,代表了一种新的途径,调节MASLD中的Treg分化.
- 这一途径为MASLD提供了潜在的治疗点.
相关概念视频
Notch Signaling Pathway
4.1K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.1K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.0K
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
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
T Cell Types and Functions
614
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...
614


