益生菌DNA在表观遗传学上调节KDM4A降解,以减轻气道过敏
Huanping Zhang1, Xiaoyao Li2, Mingxian Zhang2
1Department of Allergy Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China.
益生菌DNA通过上调USP14和KDM4A.A的调节,恢复了气道过敏 (AA) 的小鼠的1型调节性T细胞 (Tr1) 功能. 这种机制针对Tr1功能障碍,为AA提供了潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 过敏研究 研究过敏
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 1型调节性T细胞 (Tr1) 功能障碍是气道过敏 (AA) 病原体的核心.
- 在AA中底层的Tr1功能障碍的精确分子机制在很大程度上是未知的.
研究的目的:
- 在AA的小鼠模型中研究益生菌DNA在恢复Tr1细胞功能中的作用.
- 探索USP14和KDM4A在益生菌DNA介导的Tr1恢复和AA缓解中的参与.
主要方法:
- 使用灰尘虫提取物开发AA小鼠模型.
- 通过流式细胞计量评估Tr1细胞功能和Th2细胞极化.
- 通过使用ChIP和ubiquitin免疫阻塞,分析KDM4A,USP14和Il-10促进体表观遗传学.
主要成果:
- AA小鼠表现出Tr1免疫抑制受损,KDM4A在Il-10促进剂减少,Il-10促进剂高甲基化增加 (H3K9me3),USP14.
- CD4+ T 细胞中的 KDM4A 缺乏导致了自发的 Th2 气道极化和类似 AA 的病理.
- 益生菌DNA给药提高了USP14,恢复了KDM4A水平,增强了Tr1功能,并改善了小鼠的AA反应.
结论:
- 减少与Il-10促进体相关的KDM4A活性是AA中Tr1细胞功能障碍的关键驱动因素.
- 益生菌DNA通过上调USP14来减轻AA,从而恢复KDM4A功能和Tr1细胞的免疫抑制能力.
- USP14和KDM4A代表了管理气道过敏的潜在治疗点.
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