免疫细胞转录的时间动态在大脑转移的进展受肠道微生物群失生症的影响
Samantha M Golomb1, Ian H Guldner2, Emilija Aleksandrovic1
1Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, Dallas, TX 75390, USA; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA.
Cell reports
|March 2, 2025
概括
肠道微生物群的多样性影响大脑转移 (BrMet) 的进展. 改变的肠道细菌 (失生症) 恶化了BrMet,但通过便移植恢复多样性改善了结果,揭示了微生物群.
科学领域:
- 神经瘤学神经瘤学
- 免疫学 免疫学 免疫学
- 微生物组研究的研究.
背景情况:
- 大脑转移 (BrMet) 的进展受到癌细胞与大脑微环境之间的相互作用的影响.
- 中枢神经系统 (CNS) 居民和外围免疫细胞在 BrMet 免疫格局中的作用已知,但它们的调节动态尚不清楚.
- 肠道微生物群因其对中枢神经系统和外周免疫活动的影响而得到认可.
研究的目的:
- 研究肠道微生物组在调节脑转移 (BrMet) 进展期间免疫反应动态中的作用.
- 了解肠道失生症如何影响免疫环境和BrMet负担.
主要方法:
- 在小鼠模型中使用抗生素 (ABX) 诱导肠道失调.
- 便移植 (FMT) 用于恢复微生物群的多样性.
- 单细胞RNA测序以分析免疫细胞动态.
- 扰乱T细胞和微质细胞,以评估它们的作用.
主要成果:
- 与对照组相比,抗生素诱导的肠道失生症显著增加了BrMet负担.
- 便物移植使BrMet负担均等,证实了微生物组的调节作用.
- 单细胞测序揭示了动态的免疫格局,与改变的单细胞炎症反应和微质激活在晚期的BrMet在dysbiosis.
- T细胞和微质细胞调节证明了它们在肠道失生症下参与BrMet.
结论:
- 肠道微生物群的多样性显著影响大脑转移的进展和免疫反应的动态.
- 肠道功能失调症通过改变免疫细胞的时间和激活,特别是微质细胞,加剧了BrMet.
- 准肠道微生物群可能为管理大脑转移提供治疗策略.
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