糖酸突变酶通过控制血清蛋白合成和单碳代谢来调节Treg分化
Wesley H Godfrey1, Judy J Lee1, Shruthi Shanmukha2
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
eLife
|July 28, 2025
概括
糖酸盐突变酶 (PGAM) 通过控制血清蛋白合成来调节调节性T细胞 (Treg) 功能. 抑制PGAM或血清代谢会影响Treg分化和自身免疫性疾病,揭示新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 调控性CD4T细胞 (Tregs) 对于免疫抑制至关重要,并受到代谢变化的影响.
- 糖解酶在Treg功能中发挥作用,为免疫调节提供了潜在的治疗点.
研究的目的:
- 为了研究糖酸酶突变酶 (PGAM) 的作用,一个糖解酶,在Treg分化和功能.
- 探索PGAM,血清蛋白合成,一碳代谢和Treg介导的免疫抑制之间的联系.
主要方法:
- 通过药理和遗传抑制研究了PGAM在Tregs中的作用.
- 分析了PGAM抑制对Treg分化,抑制功能和T助手17 (Th17) 标记物的影响.
- 研究了血清素合成和单碳代谢在Treg极化中的作用.
- 利用多发性硬化症和自身免疫性结肠炎的小鼠模型来评估体内效应.
主要成果:
- 在Tregs中,PGAM过度表达,并与高度抑制的表型相关.
- 抑制PGAM降低了Treg分化和抑制功能,促进了类似Th17的状态.
- 来自PGAM基质 (3-糖酸) 的血清素合成对Treg功能至关重要;血清素本身抑制了Treg极化.
- 在体内改变血清水平调节了外围Tregs和减弱了实验性自身免疫疾病.
- 抑制单碳代谢增强了Treg极化和抑制功能在体外和体内.
结论:
- 在Treg分化和功能中,PGAM起着新的调节作用,与氨酸合成和单碳代谢有关.
- 代谢途径包括糖解,血清蛋白合成和单碳代谢是相互关联的,影响Treg表观遗传调节.
- 准PGAM和相关的代谢途径为自身免疫性疾病中的免疫调节提供了潜在的策略.
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