产前炎症重编程过度活跃的ILC2s,促进过敏肺炎和呼吸道功能障碍
bioRxiv : the preprint server for biology
|December 4, 2023
概括
在发育过程中产前炎症可以对免疫系统进行编程,导致过敏性喘. 这通过导致发育中的肺部特定免疫细胞过度激活而发生,从而增加了喘易感性.
科学领域:
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 过敏性喘是一种慢性呼吸道疾病,其发育起源不明.
- 产前环境因素与喘的发展有关,但具体机制尚不清楚.
研究的目的:
- 调查产前炎症如何重编程肺部免疫力,并影响过敏喘易感性.
- 确定特定免疫细胞在调解产前炎症对肺部发育和喘风险的影响中的作用.
主要方法:
- 在小鼠模型中,在胎儿发育期间诱导I型干扰素介导的炎症.
- 对免疫细胞种群,细胞因子 (IL-5,IL-13) 生产和免疫细胞功能在发育中的肺部进行分析.
- 使用暴露于产前炎症的胎儿肝脏前体的收养转移实验.
- 评估肺功能和气道过敏反应.
主要成果:
- 产前炎症导致发育中的肺部2组先天性淋巴细胞 (ILC2s) 的扩张和过度激活.
- 过度激活的ILC2s产生了IL-5和IL-13的水平升高,与Th2偏差,好色素和降低调节性T细胞 (Tregs) 相关.
- 收养转移产前炎症的胎儿前体证实了ILC2s的发育编程,导致呼吸道功能障碍和喘易感性增加.
结论:
- 产前炎症在发育过程中编程肺免疫原始体,特别是ILC2s,导致过度激活状态.
- 这种编程导致肺部免疫平衡的改变,并增加了对过敏喘的易感性.
- 这项研究确立了生命早期炎症,ILC2编程和过敏喘发展之间的直接联系.
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