美国佛罗里达大学Liang Zhou研究组发现营养对细胞内在CD71-铁轴上第3组先天淋巴样细胞(ILC3s)维持和功能中心的影响。相关论文于2023年9月14日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

他们发现转铁蛋白受体CD71(由Tfrc编码)介导的铁代谢细胞内在地控制ILC3增殖和宿主对啮齿柠檬酸杆菌感染的保护，并通过氧化磷酸化向糖酵解的转换代谢影响线粒体呼吸。铁剥夺或Tfrc消融降低ILC3中芳烃受体(Ahr)的表达和/或活性，Ahr是ILC3的关键调节因子。基因消融或激活ILC3s中的Ahr分别导致CD71上调或下调，提示Ahr介导的CD71抑制。机制上，Ahr直接结合Tfrc启动子抑制转录。铁超载部分恢复Ahr缺陷小鼠小肠中有缺陷的ILC3区室，与CD71的代偿上调一致。

这些数据共同表明Ahr-CD71-铁轴在ILC3维持和功能调节中的作用未被充分认识。

据悉，铁代谢是哺乳动物宿主细胞健康的关键，然而，其在ILC3s中的作用尚不清楚。

附：英文原文

Title: Nutrition impact on ILC3 maintenance and function centers on a cell-intrinsic CD71–iron axis

Author: Xiong, Lifeng, Helm, Eric Y., Dean, Joseph W., Sun, Na, Jimenez-Rondan, Felix R., Zhou, Liang

Issue&Volume: 2023-09-14

Abstract: Iron metabolism is pivotal for cell fitness in the mammalian host; however, its role in group 3 innate lymphoid cells (ILC3s) is unknown. Here we show that transferrin receptor CD71 (encoded by Tfrc)-mediated iron metabolism cell-intrinsically controls ILC3 proliferation and host protection against Citrobacter rodentium infection and metabolically affects mitochondrial respiration by switching of oxidative phosphorylation toward glycolysis. Iron deprivation or Tfrc ablation in ILC3s reduces the expression and/or activity of the aryl hydrocarbon receptor (Ahr), a key ILC3 regulator. Genetic ablation or activation of Ahr in ILC3s leads to CD71 upregulation or downregulation, respectively, suggesting Ahr-mediated suppression of CD71. Mechanistically, Ahr directly binds to the Tfrc promoter to inhibit transcription. Iron overload partially restores the defective ILC3 compartment in the small intestine of Ahr-deficient mice, consistent with the compensatory upregulation of CD71. These data collectively demonstrate an under-appreciated role of the Ahr-CD71–iron axis in the regulation of ILC3 maintenance and function. Iron metabolism has been shown to play an important role in the development and function of the immune system, but its role in ILC3s is unclear. Here the authors show that CD71-mediated iron metabolism controls ILC3 proliferation and the host response to Citrobacter rodentium infection and CD71 expression is regulated by Ahr signaling.

DOI: 10.1038/s41590-023-01612-z

Source: https://www.nature.com/articles/s41590-023-01612-z