在小鼠和人性化模型中,Orai抑制调节肺部ILC2代谢,并减轻呼吸道过敏反应
Emily Howard1, Benjamin P Hurrell1, Doumet Georges Helou1
1Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nature communications
|September 26, 2023
概括
(Ca2+) 释放激活的Ca2+ (CRAC) 通道组成部分Orai1和Orai2调节2组先天性淋巴细胞 (ILC2s). 阻断这些通道会降低ILC2功能和呼吸道炎症,为过敏性疾病提供治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 信号传递 信号传递
背景情况:
- 通过Ca2+释放激活Ca2+ (CRAC) 通道的 (Ca2+) 流入对免疫细胞功能至关重要.
- 2组先天性淋巴细胞 (ILC2s) 是2型炎症反应的关键驱动因素,特别是在过敏性疾病中.
研究的目的:
- 研究CRAC通道组件Orai1和Orai2在调节ILC2功能和调节气道炎症中的作用.
- 探索针对过敏呼吸道疾病的Orai1和Orai2的治疗潜力.
主要方法:
- 在小鼠ILC2s中,Orai1和Orai2的基因切除和药理阻断.
- 在小鼠呼吸道炎症模型中评估ILC2效应器功能,细胞因子产生和炎症反应.
- 评估代谢和线粒体平衡,以及ILC2s中的反应性氧物种的产生.
- 在人类ILC2s和人性化小鼠模型中验证发现.
主要成果:
- 对Orai1和Orai2的下调显著损害了ILC2效应器功能和细胞因子的产生.
- 阻断Orai1和Orai2在多个小鼠模型中改善了ILC2介导的气道炎症.
- 抑制Orai1和Orai2破坏了ILC2的代谢和线粒体平衡,增加了活性氧物种.
- 准Orai1和Orai2可以防止人性化小鼠的气道过敏反应.
结论:
- 在ILC2生物学中,Orai1和Orai2起着关键的免疫调节作用.
- 向CRAC通道组件为过敏和亚托皮性炎症性疾病提供了一个有前途的治疗策略.
- 了解ILC2s中的Ca2+信号提供了对治疗2型炎症状况的洞察力.
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