皮质醇与内分泌网膜压力协同作用,诱导调节性T细胞功能障碍
Jiangping Luo1, Caijie Zhou2, Shiqi Wang3,4,5,6,7
1Department of Chinese Traditional Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
Immunology
|July 21, 2023
概括
皮质醇和内分泌网膜 (ER) 压力通过增加Rnf20来损害食品过敏中调节性T细胞 (Treg) 功能. 抑制Rnf20恢复Treg功能,并减轻小鼠的过敏症状.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 调节性T细胞 (Tregs) 对免疫平衡和预防自身免疫性疾病至关重要.
- 功能失调的Tregs与各种免疫疾病的发病有关,包括食物过敏 (FA).
- 目前用于恢复Treg功能的治疗策略不足,需要新的方法.
研究的目的:
- 为了研究皮质醇和内质网膜 (ER) 应激对食物过敏中Treg功能的综合影响.
- 确定FA中Treg功能障碍背后的分子机制.
- 探索潜在的治疗点,以恢复FA中的Treg功能.
主要方法:
- 对食物过敏患者血清皮质醇和Treg计数的分析.
- 从FA患者的Tregs中诱导ER压力和FA的小鼠模型.
- 对Treg抑制功能和分子标记物的评估 (Rnf20,Foxp3,TGF-β).
- 在FA的体外和体外模型中对Rnf20抑制的评估.
主要成果:
- 患有FA的患者在Tregs中表现出皮质醇水平升高和ER压力,与Treg计数负相关.
- 皮质醇加剧了ER压力诱导的Treg功能障碍.
- 皮质醇和抗原特异性免疫反应诱导Tregs.中的Rnf20表达.
- 通过减少Foxp3和TGF-β表达,Rnf20抑制了Treg功能.
- 在FA患者中,Rnf20抑制恢复了Treg抑制功能,在小鼠中减弱了FA.
结论:
- 皮质醇和ER压力的协同作用通过Rnf20诱导损害了FA中的Treg功能.
- 通过降低Foxp3和TGF-β的调节,Rnf20在Treg功能障碍中起到关键的调解作用.
- 向Rnf20为恢复Treg功能和治疗FA提供了一个有希望的治疗策略.
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