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效应器Tc17细胞抵制从OXPHOS转向有氧糖解的转变

Reni John¹, Srinivasu Mudalagiriyappa¹, Nagabhushan Chandrashekar¹

¹Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, United States.

Frontiers in immunology

|June 2, 2025

概括

效应细胞Tc17,对免疫至关重要,利用氧化酸化 (OXPHOS) 获得能量,而不是糖解. 这一发现影响了针对真菌感染和自身免疫的疫苗设计和免疫疗法.

科学领域:

免疫学免疫学免疫学
细胞代谢细胞代谢
疫苗学疫苗学疫苗学

背景情况:

介素-17A (IL-17A) -表达T辅助17 (Tc17) 细胞对于免疫反应,免疫病理学和自身免疫是至关重要的.
Tc17细胞对于抗真菌免疫是必不可少的,特别是在CD4+T细胞缺乏状态下.
对于T细胞平衡至关重要的Tc17细胞的代谢适应仍然不太了解.

研究的目的:

为了研究效应器Tc17细胞所使用的代谢途径.
为了确定TC17细胞是否利用高能量的代谢途径来稳定记忆的形成 *in vivo*.

主要方法:

使用小鼠模型进行减弱的真菌疫苗接种.
将Tc17细胞的代谢活性,增殖和蛋白质合成与T辅助1 (Tc1) 细胞进行比较.
评估葡萄糖依赖性和代谢流向OXPHOS和糖解.
抑制了OXPHOS以评估其对Tc17细胞反应的影响.

主要成果:

效应细胞Tc17表现出比Tc1细胞更高的代谢活性,增殖和蛋白质合成.
Tc17细胞通过氧化酸化 (OXPHOS) 优先利用葡萄糖而不是糖解,与线粒体质量增加相关.
抑制OXPHOS显著降低了Tc17细胞反应,而Tc1细胞反应的影响较小.
Tc17细胞表现出对OXPHOS的持续依赖,抵抗适应有氧糖解.

结论:

效应Tc17细胞主要通过OXPHOS使用葡萄糖进行新陈代谢,挑战了效应T细胞中有氧糖解的教条.
这些代谢见解对于设计有效的抗真菌感染疫苗和开发用于自身免疫性疾病的免疫疗法至关重要.

关键词:

在 CD8+ T 细胞中.奥克斯福斯 (OXPHOS) 是一个在T细胞激活过程中,一个Tc17的细胞.这是一种抗真菌药物.葡萄糖溶解是什么接种疫苗的反应.

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