Abstract
After antigen stimulation, T cells preferentially increase aerobic glycolysis to meet the bioenergetic and biosynthetic demands of T cell activation, proliferation, and effector functions. Lactate, a by-product of glycolysis, has been reported to function as an important energy source and signaling molecule. Here, we found that lactate anions are involved in cytokine production in T cells after TCR activation. During ex vivo T cell activation, the addition of excess sodium lactate (NaL) increased the production of cytokines (such as IFNγ/IL-2/TNFα) more than the addition of sodium chloride (NaCl). This enhanced cytokine production was dependent on TCR/CD3 activation but not CD28 activation. In vivo, NaL treatment inhibited tumour growth in subcutaneously transplanted tumour models in a T cell-dependent manner, which was consistent with increased T cell cytokine production in the NaL treatment group compared to the NaCl treatment group. Furthermore, a mechanistic experiment showed that this enhanced cytokine production was regulated by GAPDH-mediated post-transcriptional regulation. Taken together, our findings indicate a new regulatory mechanism involved in glycolysis that promotes T cell function.
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Acknowledgements
This work was supported by the National Key Research and Development Program of China (2018YFA0507402 and 2016YFA0502202) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000).
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Wen, J., Cheng, S., Zhang, Y. et al. Lactate anions participate in T cell cytokine production and function. Sci. China Life Sci. 64, 1895–1905 (2021). https://doi.org/10.1007/s11427-020-1887-7
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DOI: https://doi.org/10.1007/s11427-020-1887-7