上腺巨细胞通过Trem2和TGF-β调节葡萄糖皮质体的产生
Yingzheng Xu1,2, Michael T Patterson1,2, Bastien Dolfi3
1Center for Immunology and.
JCI insight
|June 13, 2024
概括
上腺巨细胞通过Trem2和TGF-β调节葡萄糖皮质体的产生. 删除Trem2会增加葡萄糖皮质体的释放,这表明应激障碍的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 压力生理学 压力生理学
背景情况:
- 上腺体 (AGs) 合成的葡萄糖皮质激素对应激反应至关重要,由下丘脑-垂体-上腺轴调节.
- 在AG中的巨细胞被认为是类固醇产生的调节剂,但它们的精确分子机制仍然难以捉摸.
研究的目的:
- 研究AG巨细胞在应激反应中的作用,特别是感冒挑战和动脉样硬化炎症.
- 阐明AG巨细胞通过哪些分子机制影响葡萄糖皮质体生产.
主要方法:
- 单细胞RNA测序以分析压力下的AG巨细胞极化.
- 在巨细胞中,触发受体在骨髓状细胞2 (Trem2) 上表达的条件删除.
- 评估巨细胞死亡,TGF-β的产生和葡萄糖皮质体水平.
主要成果:
- 急性和慢性压力诱导的动态AG巨细胞偏向古典激活和脂质相关的表型.
- 在压力后,巨细胞Trem2表达得到了上调,其条件删除赋予了保护作用.
- 移除Trem2增加了AG巨细胞的死亡,取消了TGF-β的产生,并增强了葡萄糖皮质体的产生,TGF-β阻塞模仿的效果.
结论:
- 亚基巨细胞通过Trem2和TGF-β信号来限制类固醇生成.
- 针对AG巨细胞中的Trem2-TGF-β通路,为与压力相关的疾病提供了潜在的免疫治疗策略.
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