通过控制膜巨细胞存活率和亲纤维细胞活性,TREM2促进肺纤维化
Huachun Cui1, Sami Banerjee1, Na Xie1
1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Nature communications
|February 19, 2025
概括
在骨髓细胞2 (TREM2) 上表达的触发受体通过促进亲纤维细胞巨细胞的存活来驱动肺纤维化. 阻断TREM2可以缓解肺纤维化,将其确定为潜在的治疗标.
科学领域:
- 免疫学 免疫学 免疫学
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
背景情况:
- 肺部巨细胞,特别是单细胞衍生的膜巨细胞,是肺纤维化的主要驱动因素.
- 控制亲纤维细胞巨细胞行为和纤维化生存的机制尚未完全理解.
- 对肺纤维化的有效治疗策略仍然有限.
研究的目的:
- 为了研究质细胞2 (TREM2) 上表达的触发受体在肺纤维化病变的作用.
- 确定TREM2作为治疗肺纤维化的潜在治疗标.
主要方法:
- 在小鼠模型和人类异常性肺纤维化 (IPF) 肺组织中评估TREM2表达.
- 在巨细胞中利用了TREM2的遗传删除和淘汰.
- 研究了TREM2信号对巨细胞存活率,亡和亲纤维细胞表型的影响.
- 评估了TREM2阻断在肺纤维化小鼠模型中的治疗潜力.
主要成果:
- 在纤维化肺和IPF患者中,TREM2在亲纤维化单细胞衍生膜巨细胞上表达高.
- 删除或淘汰TREM2会损害巨细胞的生存信号,诱导亡,并降低它们的亲纤维活性.
- 一种特定的脂质媒介和高度的配体增强TREM2介导的巨细胞的存活率和活性.
- 使用可溶性受体或抗体阻止TREM2可显著降低小鼠肺纤维化.
结论:
- TREM2是亲纤维细胞巨细胞功能和肺纤维化中的生存的关键调节者.
- 准TREM2为治疗肺纤维化提供了一个有前途的治疗策略.
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