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Repas, J; Frlic, T; Snedec, T; Kopitar, AN; Sourij, H; Janež, A; Pavlin, M.
Physiologically Achievable Concentration of 2-Deoxy-D-Glucose Stimulates IFN-γ Secretion in Activated T Cells In Vitro.
Int J Mol Sci. 2024; 25(19): 10384 Doi: 10.3390/ijms251910384 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Sourij Harald
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Abstract:
2-deoxy-D-glucose (2DG) is a glycolysis and protein N-glycosylation inhibitor with promising anti-tumor and immunomodulatory effects. However, 2DG can also suppress T cell function, including IFN-γ secretion. Few human T cell studies have studied low-dose 2DG, which can increase IFN-γ in a Jurkat clone. We therefore investigated 2DG's effect on IFN-γ in activated human T cells from PBMCs, with 2DG treatment commenced either concurrently with activation or 48 h after activation. Concurrent 2DG treatment decreased IFN-γ secretion in a dose-dependent manner. However, 2DG treatment of pre-activated T cells had a hormetic effect on IFN-γ, with 0.15-0.6 mM 2DG (achievable in vivo) increasing and >2.4 mM 2DG reducing its secretion. In contrast, IL-2 levels declined monotonously with increasing 2DG concentration. Lower 2DG concentrations reduced PD-1 and increased CD69 expression regardless of treatment timing. The absence of increased T-bet or Eomes expression or IFNG transcription suggests another downstream mechanism. 2DG dose-dependently induced the unfolded protein response, suggesting a possible role in increased IFN-γ secretion, possibly by increasing the ER folding capacity for IFN-γ via increased chaperone expression. Overall, low-dose, short-term 2DG exposure could potentially improve the T cell anti-tumor response.
Find related publications in this database (using NLM MeSH Indexing)
Humans - administration & dosage
Interferon-gamma - metabolism
Deoxyglucose - pharmacology
Lymphocyte Activation - drug effects
T-Lymphocytes - drug effects, metabolism, immunology
Antigens, Differentiation, T-Lymphocyte - metabolism
Jurkat Cells - administration & dosage
Interleukin-2 - metabolism
Antigens, CD - metabolism
Unfolded Protein Response - drug effects
Programmed Cell Death 1 Receptor - metabolism
Lectins, C-Type - metabolism
Dose-Response Relationship, Drug - administration & dosage

Find related publications in this database (Keywords)
T cells
interferon gamma
2-deoxy-D-glucose
mitochondria
ER stress
protein N-glycosylation
CAR T
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