一个带有Notch和E2A的反放大器电路调节T细胞命运,并在胸膜本体发生过程中抑制先天性淋巴细胞系
Kazuko Miyazaki1, Kenta Horie2, Hitomi Watanabe3
1Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Genes & development
|February 4, 2025
概括
缺口信号和Id2水平控制T细胞与先天性淋巴细胞 (ILC) 的命运. 这种反回路受到小肌肉年龄的影响,通过抑制ILC发育来强制执行T细胞身份.
科学领域:
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
- 细胞信号传输 细胞信号传输
背景情况:
- T细胞和先天性淋巴细胞 (ILC) 的命运是由胸膜微环境信号和转录因子 (TF) 决定的.
- 在确定T细胞身份时,Notch1-Delta-like-4 (Dll4) 信号与E蛋白TF之间的协作机制尚未完全理解.
研究的目的:
- 阐明了关于Notch信号和E蛋白TF如何协作来确定T细胞命运的机制性见解.
- 为了确定负责胎儿和成人T细胞规范的反放大器电路.
主要方法:
- 使用了多种体内方法.
- 进行了单细胞多原子分析.
主要成果:
- 确定了一个反放大器电路,调节T细胞规范.
- 在胎儿胸腺中,最小的Notch诱导的Id2减少有利于ILC命运;高的Id2促进了ILC分化.
- 在成年胸腺中,Notch信号显著降低了Id2,增强了E蛋白活性,并激活了T细胞基因程序.
结论:
- 一个由Notch介导信号和Id2丰富度控制的反放大器电路决定了T细胞的身份.
- 这种电路抑制了胎儿和成年人胸膜环境中的先天性淋巴细胞发育.
- 通过Notch信号的Id2的差异调节有助于年龄依赖的T细胞特异化.
相关概念视频
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
Notch Signaling Pathway
4.2K
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...
4.2K
T Cell Activation and Clonal Selection
638
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
638
T Cell Types and Functions
939
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...
939
Cell Signaling Feedback Loops
6.2K
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
6.2K
B Cell Activation and Differentiation
1.6K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.6K


