ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands.,Journal of Experimental Medicine

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ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-07-11 , DOI: 10.1084/jem.20180549
Blanda Di Luccia ₁ , Susan Gilfillan ₁ , Marina Cella ₁ , Marco Colonna ₂ , Stanley Ching-Cheng Huang _{2,

3}

Affiliation

Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of Th17 that require the transcription factor RORγt for development and contribute to the defense against pathogens through IL-22 and IL-17 secretion. Proliferation and effector functions of Th17 require a specific mTOR-dependent metabolic program that utilizes high-rate glycolysis, while mitochondrial lipid oxidation and production of reactive oxygen species (mROS) support alternative T reg cell differentiation. Whether ILC3s employ a specific metabolic program is not known. Here, we find that ILC3s rely on mTOR complex 1 (mTORC1) for proliferation and production of IL-22 and IL-17A after in vitro activation and Citrobacter rodentium infection. mTORC1 induces activation of HIF1α, which reprograms ILC3 metabolism toward glycolysis and sustained expression of RORγt. However, in contrast to Th17, ILC3 activation requires mROS production; rather than inducing an alternative regulatory fate as it does in CD4 T cells, mROS stabilizes HIF1α and RORγt in ILC3s and thereby promotes their activation. We conclude that ILC3 activation relies on a metabolic program that integrates glycolysis with mROS production.

中文翻译：

ILC3 整合糖酵解和线粒体产生活性氧以满足激活需求。

第 3 组先天淋巴细胞 (ILC3) 是 Th17 的先天对应物，需要转录因子 RORγt 才能发育，并通过分泌 IL-22 和 IL-17 有助于防御病原体。 Th17 的增殖和效应功能需要特定的 mTOR 依赖性代谢程序，该程序利用高速率糖酵解，而线粒体脂质氧化和活性氧 (mROS) 的产生支持替代性 T reg 细胞分化。 ILC3 是否采用特定的代谢程序尚不清楚。在这里，我们发现 ILC3 在体外激活和啮齿类柠檬酸杆菌感染后依赖 mTOR 复合物 1 (mTORC1) 进行增殖和产生 IL-22 和 IL-17A。 mTORC1 诱导 HIF1α 激活，从而将 ILC3 代谢重新编程为糖酵解并持续表达 RORγt。然而，与 Th17 不同的是，ILC3 的激活需要 mROS 的产生； mROS 不像在 CD4 T 细胞中诱导替代的调控命运，而是稳定 ILC3 中的 HIF1α 和 RORγt，从而促进它们的激活。我们得出的结论是，ILC3 的激活依赖于将糖酵解与 mROS 产生相结合的代谢程序。

更新日期：2019-10-07

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