转录因子EGR2控制中枢神经系统中TH17细胞的归属性和致病性
Yuanyuan Gao1, Yan Wang1, Daniel Chauss2
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Nature immunology
|July 13, 2023
概括
转录因子EGR2驱动中枢神经系统 (CNS) 中的致病性T辅助者17 (TH17) 细胞,促进自身免疫性神经炎症. 向EGR2可以治疗诸如多发性硬化症之类的疾病,而不会影响免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- CD4+ T辅助17 (TH17) 细胞具有双重作用,保护组织,但也导致自身免疫.
- 控制不同组织和疾病中的TH17细胞功能的精确机制尚未完全理解.
研究的目的:
- 研究转录因子EGR2在TH17细胞致病性中的作用,特别是在中枢神经系统 (CNS).
- 探索EGR2作为自身免疫神经炎症治疗点的潜力.
主要方法:
- 对来自多发性硬化症患者和神经炎症小鼠模型的TH17细胞中EGR2表达的分析.
- 研究EGR2转录程序及其与核心TH17细胞因子的相互作用.
- 评估T细胞特异性EGR2删除对神经炎症和宿主防御的影响.
主要成果:
- 多发性硬化症患者中枢神经系统的致病性TH17细胞和小鼠模型中EGR2水平升高.
- EGR2控制中枢神经系统中的致病性TH17细胞程序,但不是屏障部位的保护性TH17细胞.
- EGR2促进TH17细胞分化和髓状细胞向中枢神经系统招募.
- 在T细胞中删除Egr2可以减少神经炎症,但不会影响感染控制.
结论:
- EGR2是致病性TH17细胞功能的关键调节者,特别是在中枢神经系统.
- EGR2调节TH17细胞的组织特异性和疾病特异性功能.
- 准EGR2为治疗诸如多发性硬化症之类的中枢神经系统自身免疫性疾病提供了一个潜在的策略.
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