通过AP-1调节轴限制先天Tγδ17细胞可塑性
Morgan E Parker1,2, Naren U Mehta1,2, Tzu-Chieh Liao1,2
1Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA.
Nature immunology
|June 27, 2025
概括
产生中白素-17 (IL-17) 的 γδ T (Tγδ17) 细胞维持肠道免疫力. 沙门氏菌感染触发Tγδ17细胞的可塑性,将它们转化为1型效应器,由JUNB/FOSL2轴调节.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 产生干白素-17 (IL-17) 的 γδ T (Tγδ17) 细胞对于肠道屏障免疫至关重要.
- 与其他IL-17产生细胞不同,Tγδ17细胞效应因子功能的可塑性和调节机制在很大程度上仍未被定义.
研究的目的:
- 定义控制Tγδ17细胞可塑性的细胞特征和调节网络.
- 研究Tγδ17细胞效应因子在恒温和感染期间的灵活性机制.
主要方法:
- 3型命运映射结合单细胞ATAC测序/RNA测序多组定型.
- 分析Tγδ17细胞的身份和功能在恒温和沙门氏菌Typhimurium感染期间.
主要成果:
- Tγδ17细胞身份通常是稳定的,但沙门氏菌感染会诱导Vγ6+ Tγδ17细胞转化为1型因子.
- 这种转化涉及IL-17A生产的丧失,RORγt下调,以及前Tγδ17细胞上的TIM-3表达.
- 确定了一个关键的AP-1调节轴 (JUNB/FOSL2),该轴控制Tγδ17细胞可塑性.
结论:
- Tγδ17细胞可塑性是肠道免疫的关键特征,允许适应感染.
- JUNB/FOSL2轴在维持Tγδ17细胞3型身份和限制1型效应因子转换方面发挥着至关重要的作用.
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