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Zinc Modulates Glutamine Metabolism in T Cells.

Authors :: Güzel N
Rink L
Fischer HJ
Source :: Molecular nutrition & food research [Mol Nutr Food Res] 2023 Oct; Vol. 67 (20), pp. e2300155. Date of Electronic Publication: 2023 Sep 01.
Publication Year :: 2023
Abstract: Scope: Zinc and glutamine are well known to be essential for the function and polarization of immune cells. T <subscript>H</subscript> 17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of T <subscript>H</subscript> 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.<br />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.<br />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.<br /> (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)