在正常和自身免疫性T依赖B细胞反应期间,CaMK4控制毛囊辅助T细胞的扩张和功能
Marc Scherlinger1,2,3, Hao Li4, Wenliang Pan4
1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. marc.scherlinger@chru-strasbourg.fr.
Nature communications
|January 29, 2024
概括
/卡尔莫杜林依赖的蛋白激酶IV (CaMK4) 在自身免疫中驱动T毛囊辅助细胞 (Tfh) 扩张. 这种CaMK4/CREMα通路损害了B细胞的调节,导致系统性红斑狼 (SLE) 中的自身抗体的产生.
科学领域:
- 免疫学 免疫学 免疫学
- 这是自身免疫力.
- 分子生物学分子生物学
背景情况:
- 系统性红斑狼 (SLE) 涉及B细胞失调和自身抗体的产生.
- 毛囊T辅助细胞 (Tfh) 对于B细胞激活和抗体反应至关重要.
研究的目的:
- 研究/卡尔莫杜林依赖蛋白激酶IV (CaMK4) 在Tfh细胞扩张和自身免疫中的作用.
- 阐明将CaMK4与Tfh细胞功能和B细胞失调联系起来的分子机制.
主要方法:
- 在免疫和自身免疫的小鼠模型中研究了T细胞特异的CaMK4表达.
- 利用分子分析来确定CaMK4通过CREMα对Bcl6转录的控制.
- 在野生型和CaMK4缺乏的小鼠中评估了Tfh细胞功能,生殖中心的形成和自身抗体的产生.
- 研究了对人类Tfh细胞的CaMK4抑制作用,以及SLE患者中与BCL6相关的CAMK4mRNA水平.
主要成果:
- 在免疫和自身免疫模型中,T细胞特异性的CaMK4表达促进了Tfh细胞扩张.
- CaMK4通过CREMα调节Tfh特异性转录因子Bcl6.
- 在易患狼的小鼠中,CaMK4缺乏会损害生殖中心形成,幽默免疫力,减少自身抗体和沉积.
- 抑制CaMK4减少了BCL6,IL-21分泌,血质细胞的形成和人类Tfh细胞中的IgG产生.
- 在SLE患者的Tfh细胞中,CAMK4mRNA水平与BCL6相关.
结论:
- CaMK4是Tfh细胞扩张和功能的一个关键驱动因素.
- 已确定CaMK4/CREMα通路是T细胞依赖B细胞失调在自身免疫中的关键调节者.
- 向CaMK4可能为SLE和其他自身免疫性疾病提供治疗策略.
更多相关视频
07:07Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
5.3K
07:39Isolation of CD4+ T-cells and Analysis of Circulating T-follicular Helper cTfh Cell Subsets from Peripheral Blood Using 6-color Flow Cytometry
Published on: January 7, 2019
12.3K
相关概念视频
01:24T Cell Types and Functions
1.0K
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...
1.0K
01:22T Cell Activation and Clonal Selection
735
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...
735
01:27Cytotoxic T Cells-mediated Immune Response
917
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...
917