Nergis Güzel, Lothar Rink, Henrike Josephine Fischer
{"title":"锌对T细胞谷氨酰胺代谢的调节作用。","authors":"Nergis Güzel, Lothar Rink, Henrike Josephine Fischer","doi":"10.1002/mnfr.202300155","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Scope</h3>\n \n <p>Zinc and glutamine are well known to be essential for the function and polarization of immune cells. T<sub>H</sub>17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of T<sub>H</sub>17 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.</p>\n </section>\n \n <section>\n \n <h3> Methods and results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"67 20","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202300155","citationCount":"0","resultStr":"{\"title\":\"Zinc Modulates Glutamine Metabolism in T Cells\",\"authors\":\"Nergis Güzel, Lothar Rink, Henrike Josephine Fischer\",\"doi\":\"10.1002/mnfr.202300155\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Scope</h3>\\n \\n <p>Zinc and glutamine are well known to be essential for the function and polarization of immune cells. T<sub>H</sub>17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of T<sub>H</sub>17 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods and results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":212,\"journal\":{\"name\":\"Molecular Nutrition & Food Research\",\"volume\":\"67 20\",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202300155\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Nutrition & Food Research\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202300155\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"FOOD SCIENCE & TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Nutrition & Food Research","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202300155","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
Zinc and glutamine are well known to be essential for the function and polarization of immune cells. TH17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of TH17 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.
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.
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