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Updated: Jul 17, 2025

Glutamine Flux Imaging Using Genetically Encoded Sensors
Published on: July 31, 2014
Zinc Modulates Glutamine Metabolism in T Cells
Nergis Güzel1, Lothar Rink1, Henrike Josephine Fischer1
1Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
Scope:
Zinc and glutamine are well known to be essential for the function and polarization of immune cells. TH 17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of TH 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.
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.
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