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表皮细胞膜的穿孔诱发过敏的呼吸道炎症
Kejian Shi1,2, Yao Lv2,3, Chunqiu Zhao4,5
1School of Life Sciences, Beijing Normal University, Beijing, China.
Nature
|July 31, 2025
概括
像真菌这样的过敏原中形成毛孔的蛋白质可以通过在呼吸道细胞中形成毛孔来引发过敏性呼吸道炎症. 这一发现揭示了各种过敏原的共同机制, 并提出了新的过敏治疗点.
科学领域:
- 免疫学
- 分子生物学
- 对过敏的研究
背景情况:
- 过敏性呼吸道炎症是由激活2型免疫反应的各种过敏原引起的.
- 呼吸道上皮细胞是检测过敏原的关键,但它们的共同特征和检测机制尚不清楚.
研究的目的:
- 识别各种过敏原引发过敏呼吸道炎症的共同特征.
- 阐明这些过敏原在上皮细胞水平上的免疫激活机制.
主要方法:
- 模具过敏原Alternaria alternata的生物化学分化以分离免疫刺激成分 (Aeg-S和Aeg-L).
- 用冷电子显微镜来确定孔综合体的结构.
- 在体外和体内 (小鼠模型) 实验中评估毛孔形成活性在过敏反应中的作用.
- 对A. alternata进行基因工程,以制造缺乏毛孔形成活动的菌株.
主要成果:
- 形成毛孔的蛋白质 (Aeg-S和Aeg-L) 被确定为核心免疫刺激成分,形成跨膜毛孔复合体.
- 这些毛孔复合物作为免疫辅助剂,增强T助手2和免疫球蛋白E反应.
- 缺乏毛孔形成活性的A. alternata菌株在小鼠中没有引起过敏反应.
- 不同物种的毛孔形成蛋白质足以引发呼吸道过敏,无论结构上的差异如何.
结论:
- 形成毛孔的蛋白质是导致过敏呼吸道炎症的常见刺激.
- 这些蛋白质对上皮细胞的穿孔通过IL-33释放和Ca2+流入介导的MAPK信号发出过敏反应.
- 针对上皮层穿孔信号通路为呼吸道过敏提供了潜在的新治疗策略.
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