在CD8+ T细胞中,通过介质素2-可诱导的T细胞激酶 (ITK) 调节TCR诱导的转录动力学
Josh Hunkins1, Zoe K Bedrosian1, Uddeep Chaudhury1
1Department of Immunology/Microbiology, University of Colorado CU Anschutz, Denver, CO.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
氨酸激酶ITK (氨酸二诱导性T细胞激酶) 对于终止T细胞受体信号传递至关重要. 它的缺失导致持续的T细胞激活,影响几天后的基因表达.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 纯粹的CD8+T细胞激活涉及NFAT,NFκB和AP-1转录因子,主要由T细胞受体 (TCR) 信号调节.
- 泰克家族氨酸激酶ITK影响了这些转录因子激活的动力学和大小,这些激活在TCR的下游.
研究的目的:
- 研究ITK信号在调节CD8+T细胞中TCR信号的持续和终止中的作用.
- 了解ITK如何调节TCR依赖转录反应的时间动态.
主要方法:
- 使用"Nr4a3-Tocky"记者鼠标长时间监测TCR信号动力学.
- 在多个时间点刺激OT-I CD8+ T细胞,具有不同的联体亲和力,并分析了多个时间点的表面/细胞内标记物.
- 使用双ITK/RLK抑制剂 (PRN694) 在激活后的前24小时内评估ITK的功能.
主要成果:
- 正如预期的那样,ITK信号增强了早期T细胞激活标志物的动力学和大小.
- 缺少ITK导致了几种蛋白质在以后的时间点持续表达,这表明它在TCR信号终止中的作用.
- 发现ITK对TCR信号的负调节功能在T细胞激活后的最初24小时内是必需的.
结论:
- 在CD8+ T细胞中,ITK在终止TCR依赖的转录反应中起着至关重要的作用.
- 这种ITK介导的负调节是在T细胞激活的早期建立的,但对基因表达模式有长期的影响.
- 研究结果揭示了一种编程的机制,在初始激活几天后影响CD8+T细胞的反应.
相关概念视频
T Cell Activation and Clonal Selection
14.8K
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...
14.8K
T Cell Types and Functions
2.2K
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...
2.2K
Cytotoxic T Cells-mediated Immune Response
6.5K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.5K
The JAK-STAT Signaling Pathway
12.1K
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...
12.1K
Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
TGF - β Signaling Pathway
10.5K
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...
10.5K


