Zinc Modulates Glutamine Metabolism in T Cells

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Molecular Nutrition & Food Research Pub Date : 2023-09-01 DOI:10.1002/mnfr.202300155

Nergis Güzel, Lothar Rink, Henrike Josephine Fischer

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Abstract

Scope

Zinc and glutamine are well known to be essential for the function and polarization of immune cells. T_H17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of T_H17 cells can contribute to the development of autoimmune diseases. Both inhibition of glutaminolysis and zinc supplementation suppress experimental autoimmune encephalomyelitis in mice. Therefore, the aim of this study is to investigate whether zinc modulates glutaminolysis in T cells.

Methods and results

CD3/CD28 stimulation and mixed lymphocytes culture are used as in vitro models for T cell activation. Then, the glutaminolysis is investigated on mRNA, protein, and functional level. Zinc deficiency and glutaminase (GLS) inhibition decrease immune responses in vitro. Furthermore, extracellular zinc and glutamine levels both modulate glutaminolysis by changing the expression of glutamine transporters and key enzymes. Intriguingly, zinc directly interferes with the activity of GLS both in a cell free system and in the cytosol.

Conclusion

Besides T cell subset differentiation, zinc also impacts on the cellular metabolism by inhibiting glutaminolysis. This suggests that zinc deficiency can contribute to the development of autoimmune diseases whereas zinc supplementation can support their therapy.

Abstract Image

查看原文本刊更多论文

锌对T细胞谷氨酰胺代谢的调节作用。

范围：众所周知，锌和谷氨酰胺对免疫细胞的功能和极化至关重要。TH 17细胞在缺锌期间更频繁地被诱导，并且主要通过谷氨酰胺分解来满足其能量需求。TH 17细胞的失调可能导致自身免疫性疾病的发展。抑制谷氨酰胺分解和补充锌都能抑制小鼠实验性自身免疫性脑脊髓炎。因此，本研究的目的是研究锌是否调节T细胞中的谷氨酰胺分解。方法和结果：CD3/CD28刺激和混合淋巴细胞培养作为T细胞活化的体外模型。然后，从信使核糖核酸、蛋白质和功能水平对谷氨酰胺裂解进行了研究。锌缺乏和谷氨酰胺酶（GLS）抑制降低体外免疫反应。此外，细胞外锌和谷氨酰胺水平都通过改变谷氨酰胺转运蛋白和关键酶的表达来调节谷氨酰胺水解。有趣的是，锌在无细胞系统和胞质溶胶中都直接干扰GLS的活性。结论：除了T细胞亚群分化外，锌还通过抑制谷氨酰胺分解作用影响细胞代谢。这表明锌缺乏会导致自身免疫性疾病的发展，而锌补充可以支持其治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.