低氧暴露促进Th17细胞通过Activin A-PKM2轴的分化,以加剧自身免疫和自身炎症性疾病
Yuhui Li1, Mengting He1, Jie Xu1
1Phenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
概括
高海拔 (低压性缺氧) 通过增加致病性Th17细胞,使自身免疫性疾病恶化. 活性蛋白A通过ERK通路驱动这一过程,为高海拔免疫障碍提供治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 高海拔的生理学 高海拔的生理学
- 疾病的分子机制.
背景情况:
- 高海拔 (低压性缺氧) 改变了免疫反应和疾病微环境.
- 自身免疫和自身炎症性疾病可能会受到高海拔条件的独特影响.
研究的目的:
- 调查催性缺氧对自身免疫和自身炎症性疾病的影响.
- 阐明这些在高海拔地区的免疫反应背后的分子机制.
主要方法:
- 实验性自身免疫脑膜炎 (EAE) 和牛皮的小鼠模型被暴露在模拟的6000米高度.
- 使用了病理学分析,流细胞计,转录组学和药理学抑制.
- 分析了包括Activin A,ERK和p-PKM2在内的关键分子通路.
主要成果:
- 低压性缺氧加剧了EAE和牛皮的严重程度,增加了致病的Th17细胞.
- 活性蛋白A被确定为低氧诱导的Th17分化的关键调节剂.
- 抑制Activin A或阻断ERK/p-PKM2信号改善了疾病的严重程度.
结论:
- 低氧触发的Activin A释放通过ERK/p-PKM2通路驱动致病性Th17分化.
- 这种机制有助于高海拔地区的免疫失调.
- 向Activin A为与高海拔相关的免疫疾病提供了潜在的治疗策略.
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