一个T-bet梯度控制CCR6-RORγt+先天性淋巴细胞的命运和功能
Christoph S N Klose1, Elina A Kiss, Vera Schwierzeck
1Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
Nature
|January 22, 2013
概括
转录因子T-bet指导先天性淋巴细胞 (ILC) 产生干扰素- (IFN-γ),这对抗沙门氏菌的屏障保护至关重要. 这个T-bet表达式在RORγt(+) ILC中平衡了宿主防御和病理.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 粘膜免疫反应必须耐受环境抗原,同时对抗病原体.
- 免疫细胞可塑性的转录调节,从恒常状态到抗微生物免疫力是不太了解的.
- 固有的淋巴细胞 (ILC) 是肠道免疫的关键参与者,但它们的子集规格尚不清楚.
研究的目的:
- 确定控制RORγt ((+) ILC子集命运和功能的转录调节剂.
- 阐明T-bet在特定RORγt ((+) ILC血统的分化和功能中的作用.
- 了解T-bet表达ILCs在沙门氏菌感染期间对宿主防御和病理学的贡献.
主要方法:
- 在不同的ILC子集中对转录因子表达 (T-bet,RORγt) 的分析 (CCR6(-) 与CCR6(+)).
- 研究影响T-bet表达的因素,包括开始性微生物群和IL-23.
- 在沙门氏菌肠道感染的小鼠模型中进行基因操纵 (T-bet缺陷) 和细胞枯竭研究.
主要成果:
- T-bet表达式定义了一种独特的CCR6 ((-) RORγt (((+) ILCs血统,由微生物群和IL-23产后诱导.
- T-bet驱动IFN-γ和NKp46的表达,使其能够分化为NK-22细胞.
- 在T-bet缺乏的小鼠中,在沙门氏菌感染期间,ILCs的IFN-γ产量受损,粘液产量减少,以及较轻微的肠球炎.
结论:
- T-bet作为IFN-γ产生CCR6的差异化的一个关键决定因素.
- 这些表达T-bet的ILCs通过促进粘液分泌,对抗沙门氏菌的上皮屏障完整性至关重要.
- T-bet和RORγt的共同表达代表了平衡天生的防御和免疫介导病理的保存程序.
更多相关视频
11:50Retroviral Transduction of Helper T Cells as a Genetic Approach to Study Mechanisms Controlling their Differentiation and Function
Published on: November 4, 2016
11.6K
05:03Author Spotlight: Elucidating the Pathways of TFH Cell Differentiation in Acute LCMV Challenges
Published on: April 26, 2024
1.5K
相关概念视频
01:22T Cell Activation and Clonal Selection
13.7K
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...
13.7K
01:24T Cell Types and Functions
3.2K
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...
3.2K