Lactate anions participate in T cell cytokine production and function
- 9 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Science China Life Sciences
- Vol. 64 (11), 1895-1905
- https://doi.org/10.1007/s11427-020-1887-7
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.Keywords
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