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 Medical Center, Durham, NC, USA.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
产生IL-17的玛三角T (Tγδ17) 细胞可以在感染期间改变其功能. 一个关键的AP-1调节轴控制这种可塑性,稳定它们的免疫反应并防止不必要的细胞转化.
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:
- 玛三角形T (Tγδ) 细胞,特别是IL-17产生Tγδ17细胞,对于肠道屏障免疫至关重要.
- 与已被充分研究的Th17细胞和先天性淋巴细胞 (ILC) 不同,调节Tγδ17细胞可塑性的机制尚不清楚.
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.
- 为了研究Tγδ17细胞效应器功能在响应刺激时的灵活性.
主要方法:
- 采用了3型命运映射与单细胞ATAC/RNA-seq多基因分析相结合.
- 在平衡和*S. typhimurium*感染期间分析了Tγδ17细胞群.
主要成果:
- 在恒常状态期间,Tγδ17细胞身份是稳定的,但Vγ6+Tγδ17细胞在*S. typhimurium*感染时转化为1型因子,失去IL-17A的产生.
- 单细胞多基因组分析发现了由TIM-3标记的转化轨迹,表明前Tγδ17细胞的增强型1功能.
- 一个关键的AP-1调节轴涉及JunB和Fosl2被确定为控制Tγδ17细胞可塑性.
结论:
- AP-1轴 (JunB/Fosl2) 稳定了Vγ6+ Tγδ17细胞的3型身份,限制了它们转化为1型效应器.
- 这项研究阐明了在肠道免疫反应中Tγδ17细胞效应器灵活性背后的分子机制.
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