在记忆驱动喘中,NFκB1抑制记忆形成,并支持ILC2s的效应器功能
Mukesh Verma1, Divya Verma1, Anand Santosh Sripada1
1Division of Allergy & Immunology, Department of Medicine, National Jewish Health, Denver, CO, United States.
Frontiers in immunology
|August 14, 2023
概括
核因子kappa B亚单元1 (NFκB1) 驱动喘效应因子反应,但抑制了ILC2s的记忆诱导. 这突显了训练免疫力中记忆形成和效应器功能之间的关键平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 过敏和喘研究研究
- 天生免疫记忆天生的免疫记忆
背景情况:
- 2组先天性淋巴细胞 (ILC2s) 可以发展记忆,但控制ILC2记忆诱导和训练免疫的机制仍然不清楚.
- 在ILC2s中NFκB1的高表达表明在这些过程中可能发挥作用.
研究的目的:
- 在喘小鼠模型中调查NFκB1在ILC2记忆诱导和记忆驱动的效应器功能的作用.
- 阐明NFκB1在ILC2-介导过敏炎症中的功能背后的分子机制.
主要方法:
- 通过鼻内注射Alternaria诱导喘模型.
- 通过使用柔性检测,ELISA,组织学,实时PCR,西斑,流细胞计和免疫光染色来评估免疫反应.
主要成果:
- NFκB1对于记忆驱动性喘的效应阶段至关重要,促进IL33的产生,ILC2的产生和2型细胞因子的释放,导致eosinophilic炎症.
- 在ILC2s的2型细胞因子诱导中NFκB1的作用是独立于GATA3.3.
- NFκB1也会影响过敏原诱导的ILC3s和FoxP3+Tregs,但不会影响Th2细胞.
- 相反,NFκB1通过抑制ILC2s中的记忆相关基因上调来对抗记忆诱导,并促进RUNX1的上调,与RUNX1.1形成异构体.
结论:
- NFκB1表现出双重作用,积极调节效应器阶段,同时抑制ILC2s中的记忆诱导阶段.
- 记忆诱导和效应过程之间存在着相互依存的对立.
- NFκB1-RUNX1异构体作为ILC2s中的2型细胞因子的非正规转录激活剂.
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