| Title: | Physiologically achievable concentration of 2-deoxy-D-glucose stimulates IFN-γ secretion in activated T cells in vitro |
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| Authors: | ID Repas, Jernej (Author)
ID Frlic, Tjaša (Author)
ID Snedec, Tadeja (Author)
ID Kopitar, Andreja Nataša (Author)
ID Sourij, Harald (Author)
ID Janež, Andrej (Author)
ID Pavlin, Mojca (Author) |
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| Files: |  PDF - Presentation file, download (2,76 MB)
MD5: 19B42B5FE600868704B0564989C0F230
 URL - Source URL, visit https://www.mdpi.com/1422-0067/25/19/10384
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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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. |
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| Keywords: | T cells, interferon gamma, 2-deoxy-D-glucose |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 1-21 |
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| Numbering: | Vol. 25, iss. 19 , [article no.] 10384 |
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| PID: | 20.500.12556/DiRROS-29992  |
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| UDC: | 616.379 |
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| ISSN on article: | 1422-0067 |
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| DOI: | 10.3390/ijms251910384 |
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| COBISS.SI-ID: | 208868867 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 30. 9. 2024;
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| Publication date in DiRROS: | 11.06.2026 |
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| Views: | 206 |
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| Downloads: | 186 |
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