对Foxp3转录因子在调控性T细胞中的表达的时间和上下文依赖的要求
Wei Hu1,2,3, Gabriel Dolsten4, Giorgi Beroshvili1,5
1Howard Hughes Medical Institute, Immunology Program, and Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Research square
|June 5, 2025
概括
调节性T (Treg) 细胞需要转录因子Foxp3进行免疫抑制. 福克斯p3对于Treg早期发育至关重要,但对于成熟细胞来说不那么重要,除了在瘤中,其损失会损害功能和生长.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 通过Foxp3表达定义的调节性T (Treg) 细胞对于免疫平衡至关重要.
- 通过Foxp3调节Treg转录网络的确切机制尚未完全阐明.
研究的目的:
- 为了研究Treg细胞中Foxp3的特定阶段功能.
- 了解Foxp3在维护Treg转录程序和不同环境中的抑制功能中的作用.
主要方法:
- 利用一种新的化学遗传系统,在体内诱导Foxp3蛋白质的时间控制降解.
- 在各种Treg发育阶段和瘤微环境中,分析了Foxp3耗尽后的转录变化和抑制能力.
主要成果:
- 福克斯p3对于Treg转录编程和抑制在胸膜前代细胞和新形成的外围Treg细胞中是不可或缺的.
- 成熟的Treg细胞中Foxp3的降解导致了最小的转录性改变,并保持了抑制能力.
- 瘤Treg细胞对Foxp3损失表现出独特的敏感性,导致抑制受损并抑制瘤生长.
结论:
- 在Treg细胞中对Foxp3的要求取决于环境,在不同的发育阶段和生理/病理条件下有所不同.
- 福克斯p3的作用对于确定Treg的身份和功能至关重要,但在成熟细胞中,它的必要性减少,在瘤微环境中显著的例外.
相关概念视频
T Cell Types and Functions
963
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...
963
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
General Transcription Factors
5.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.2K


