抑制性共受体Lag3通过抑制Myc依赖的代谢编程来支持Foxp3+调节性T细胞功能
Dongkyun Kim1, Giha Kim1, Rongzhen Yu1
1Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Immunity
|September 5, 2024
概括
淋巴细胞激活基因3 (Lag3) 对于调节T (Treg) 细胞功能在控制自身免疫方面至关重要. Lag3通过调整Myc-依赖的途径来调节Treg细胞代谢和抑制活性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 淋巴细胞激活基因3 (Lag3) 是激活的T细胞上的抑制性共受体.
- 它在调节调节性T (Treg) 细胞功能中的作用尚未完全理解.
- Lag3在免疫调节中的精确机制仍然难以捉摸.
研究的目的:
- 调查Lag3在Treg细胞功能和自身免疫力中的作用.
- 阐明 Lag3 影响 Treg 细胞活动的分子机制.
- 为了确定由Treg细胞中的Lag3调节的关键通路.
主要方法:
- 产生特异于Treg细胞的Lag3突变小鼠模型.
- RNA测序分析以识别突变Treg细胞中改变的基因表达.
- 对酸氨基 3-激酶 (PI3K) -Akt-Rictor通路和Myc目标的研究.
主要成果:
- Lag3对于Treg细胞对自身免疫的控制至关重要.
- Lag3突变改变了代谢过程,特别是在Treg细胞中显著增加了Myc目标基因表达.
- 增加的Myc表达与改变的代谢概况和受损的体内抑制功能相关.
- 在Lag3突变Treg细胞中观察到PI3K-Akt-Rictor通路的激活.
- 抑制PI3K,Rictor或乳酸脱酶A (Ldha) 恢复了正常的Treg细胞代谢和功能.
结论:
- 拉格3在Treg细胞介导的自身免疫控制中起着至关重要的作用.
- Lag3通过调节Myc-依赖的代谢编程来支持Treg细胞抑制功能.
- 针对Myc-Ldha等代谢途径可能是免疫调节的治疗策略.
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