20.500.12556/DiRROS-29992 Physiologically achievable concentration of 2-deoxy-D-glucose stimulates IFN-γ secretion in activated T cells in vitro 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. T cells interferon gamma 2-deoxy-D-glucose celice T interferon gama 2-deoksi-D-glukoza true false true Angleški jezik Slovenski jezik Neznano 2026-06-11 09:40:19 2026-06-11 09:40:19 2026-06-12 03:54:41 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 30. 9. 2024; str. 1-21 iss. 19 , [article no.] 10384 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.379 1422-0067 10.3390/ijms251910384 208868867 RAZ_Repas_Jernej_2024.pdf RAZ_Repas_Jernej_2024.pdf 1 19B42B5FE600868704B0564989C0F230 f907ba741c16f5202a0de4370c6f5b4c2ca254e9e4dbbe903332cc18d659df42 e99231b7-6568-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45190 https://www.mdpi.com/1422-0067/25/19/10384 1 cce3eec3-6568-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45189 Univerzitetni klinični center Ljubljana 0 0 0