Metabolic Blockade of Glycolysis Diminishes Autoreactive CD4 T-Cell Effector Responses in Type 1 Diabetes.

Chávez, Miranda D; Mahr, Anna R; Wilkins, Heather M; Tse, Hubert M · Diabetes · 2026

basic_science · Level V

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Abstract

Our goal: limit glycolysis with 2-deoxyglucose (2-DG) in autoreactive CD4 T cells to delay spontaneous type 1 diabetes in NOD mice. Inhibition of glycolysis with 2-DG during autoreactive CD4 T-cell activation and differentiation decreased effector responses (interferon-γ), increased anergic markers (CD73, folate receptor 4), and delayed spontaneous type 1 diabetes in NOD mice. The effects of 2-DG on antigen-presenting cells resulted in a decrease in CD86 expression that may partly explain the induction of anergy. Inhibiting glycolysis is sufficient to diminish autoreactive CD4 T-cell responses and may be therapeutically applicable to other T cell-mediated inflammatory diseases.