胆汁酸的细菌代谢促进了外围调节T细胞的产生
Clarissa Campbell1, Peter T McKenney2,3, Daniel Konstantinovsky4
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. campbec2@mskcc.org.
Nature
|May 29, 2020
概括
二次胆酸isoDCA促进了肠道中调节性T细胞 (Treg细胞) 的发展. 这一过程涉及特定的微生物群体,并增强了Treg细胞的异化.
科学领域:
- 免疫学
- 微生物学
- 胃肠病学
背景情况:
- 肠道健康取决于通过Foxp3表达定义的CD4+调节T细胞.
- 外围Treg (pTreg) 细胞诱导受微生物代谢物如丁酸盐的影响.
- 细菌将宿主分子,如胆酸转化为生物活性物质.
研究的目的:
- 选脱胆酸以检测它们促进pTreg细胞分化的能力.
- 研究胆汁酸影响Treg细胞生成的机制.
- 通过工程微生物联盟探索特定胆汁酸的体内效应.
主要方法:
- 检测脱胆酸对Foxp3诱导的影响.
- 研究树突细胞 (DC) 和法内索体X受体 (FXR) 的作用.
- 使用合成生物学与工程 Bacteroides 菌株在体内产生特定的胆汁酸.
主要成果:
- 二次胆汁酸3β-氧脱氧醇酸 (isoDCA) 增强了T细胞中的Foxp3诱导.
- isoDCA作用于DCs,降低它们的免疫刺激特性.
- 在DC中切除FXR模仿了isoDCA对Treg细胞生成的影响.
- 产生IsoDCA的微生物群体以CNS1依赖的方式增加了结肠RORγt表达的Treg细胞.
结论:
- 胆汁酸IsoDCA促进了Treg细胞的异化.
- isoDCA的机制涉及调节直流功能,可能通过FXR.
- 工程微生物联盟可以利用胆酸代谢来影响结肠免疫细胞群.
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