改变的微生物胆汁酸代谢加剧了T细胞驱动的炎症在移植对宿主疾病期间
Sarah Lindner1, Oriana Miltiadous2, Ruben J F Ramos3
1Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature microbiology
|March 1, 2024
概括
微生物胆汁酸代谢影响免疫健康. 在移植与宿主疾病 (GVHD) 中,减少的胆酸会恶化炎症,而阻断FXR则可以防止GVHD.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 胃肠病学 胃肠病学
背景情况:
- 胆汁酸的微生物转化会影响免疫的恒常性.
- 这些转变在诸如移植与宿主疾病 (GVHD) 等炎症性疾病中的作用尚不清楚.
研究的目的:
- 为了研究T细胞驱动炎症对GVHD中的胆酸代谢的影响.
- 确定Farnesoid X受体 (FXR) 在GVHD病变发生中的作用.
主要方法:
- 使用GVHD.的小鼠模型.
- 分析了微生物组编码的胆盐酸酶 (BSH) 基因丰度和胆酸水平.
- 研究了在供体T细胞中FXR激活和消灭的影响.
- 在人类GVHD患者中检查了BSH和胆酸水平.
主要成果:
- 在GVHD中由T细胞驱动的炎症减少了BSH基因和未结合胆酸.
- 微生物衍生胆酸的损失与增加的FXR活性相关.
- 药理性FXR激活加剧了GVHD死亡率,而基因切除保护了小鼠.
- 人类GVHD患者表现出类似的BSH损失和胆酸减少.
- 乌尔索西胆酸 (FXR抗剂) 降低了人类T细胞的增殖和与GVHD相关的死亡率.
结论:
- 失生症和微生物衍生的胆酸的损失会放大T细胞介导的疾病,如GVHD.
- 在T细胞中的FXR信号传递是GVHD进展的关键因素.
- 向胆酸代谢和FXR可能为GVHD提供治疗策略.
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