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营养对ILC3维护和功能中心在细胞内在的CD71-铁轴上的营养影响

Lifeng Xiong¹, Eric Y Helm¹, Joseph W Dean¹

¹Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.

Nature immunology

|September 14, 2023

概括

通过CD71调节的铁代谢对3组先天性淋巴细胞 (ILC3) 至关重要. 这一途径影响ILC3的增殖,宿主防御和代谢功能,揭示了一个新的调节轴.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
代谢过程中的代谢.

背景情况:

铁代谢对于哺乳动物细胞功能至关重要.
铁在3组先天性淋巴细胞 (ILC3s) 中的作用以前是未知的.
第三组先天性淋巴细胞 (ILC3s) 对于宿主防御和组织平衡至关重要.

研究的目的:

研究铁代谢在ILC3扩散和功能中的作用.
阐明将铁代谢与ILC3调节联系起来的分子机制.
确定铁代谢,酸受体 (Ahr) 和ILC3s之间的相互作用.

主要方法:

在ILC3s中使用了基因切除或操纵转移素受体CD71 (Tfrc) 和酸受体 (Ahr) 的小鼠模型.
评估了ILC3的扩散,对宿主抗击Citrobacter rodentium感染的保护,以及线粒体呼吸.
分析了基因表达,蛋白质活性和Ahr与Tfrc基因的直接促进体结合.

主要成果:

CD71介导的铁代谢本质上控制着ILC3的增殖和宿主保护.
在ILC3s中,缺铁或Tfrc除会降低Ahr表达/活性.
艾尔直接抑制Tfrc转录,铁过载可以在艾尔缺乏的小鼠中拯救ILC3缺陷.

结论:

Ahr-CD71-铁轴是ILC3维护和功能的一个关键调节器.
这一途径影响ILC3的代谢重编程,从氧化酸化到糖解.
了解这个轴可以了解免疫细胞的健康状况和宿主防御机制.

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