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  • Physiologically achievable concentration of 2-deoxy-D-glucose stimulates IFN-γ secretion in activated T cells in vitro [Elektronski vir]
    Repas, Jernej ...
    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.
    Source: International journal of molecular sciences [Elektronski vir]. - ISSN 1422-0067 (Vol. 25, iss. 19 , [article no.] 10384, 2024, str. 1-21)
    Type of material - e-article ; adult, serious
    Publish date - 2024
    Language - english
    COBISS.SI-ID - 208868867

    Link(s):

    https://www.mdpi.com/1422-0067/25/19/10384
    DOI

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