2-DG Re-Normalized IFN-γ Production in T Cells Excluding T_EMRA Cells from Patients with Aplastic Anemia

ABSTRACT

Aplastic anemia (AA) is a T cell immune mediated autoimmune disease in which cytokines, particularly IFN-γ are pathogenesis factors. Glucose metabolism is closely related to effector functions of activated T cells, such as IFN-γ production. The characteristics of glucose metabolism and whether interfering with glucose metabolism could affect T cells produce IFN-γ ability in AA patients remains unknown. In this study, we examined the characteristics of glucose metabolism in T cells from AA patients and the effects of the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG) on the ability of T cell production IFN-γ. Our data demonstrated abnormal glucose metabolism in stimulated T cells from AA patients, mainly reflected by increased glucose uptake and lactate secretion. In addition, EM and T_EMRA cells exhibit higher glucose uptake in patients with AA compared with healthy individuals. Moreover, the frequency of IFN-γ⁺ was reduced by 2-DG in T cell from AA patients. Unexpectedly, 2-DG re-normalized the frequency of IFN-γ⁺ in other T cell subsets, except for in the T_EMRA. In conclusion, our study reveals for the first time the existence of enhanced aerobic glycolysis in T cells from AA patients, and different T cell subsets exhibit different extent glucose uptake requirements. Aerobic glycolysis regulation may be a potential therapeutic strategy for aberrant T cell immunity. Moreover, T_EMRA may have specific metabolic abnormalities, which should receive more attention in future targeted immune metabolism research.

GRAPHICAL ABSTRACT

KEYWORDS:

• Aplastic anemia
• 2-deoxy-D-glucose
• effector memory cells re-expressing CD45RA cells
• interferon γ

Acknowledgments

We want to thank the flow facility of the Institute of Aging and Regenerative Medicine, Jinan University. We would also like to thank the volunteers who donated blood for this project.

Author contributions

BL and YQL contributed to the concept development, provided the study design, coordinate the study, and drafted the manuscript. YZ and XQL performed the laboratory studies, contributed to the data analysis, and prepared the figures and table. YPZ, XHC, YKZ, XEL, and SJW provided the samples and clinical data. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

All PB samples were obtained with consent. The study was approved by the Ethics Committee of School of Medicine of Jinan University. Written informed consent was obtained from patients in accordance with the Helsinki Declaration.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [No. 82270140] and the Natural Science Foundation of Guangdong province [No. 2020A151501042]