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Lactate anions participate in T cell cytokine production and function

Science China(Life Sciences) 2021年第11期64卷 1895-1905页

作者： Jing Wen Shipeng Cheng Yaguang Zhang Ran Wang Jiefang Xu Zhiyang Ling Liyan Ma Xinghao Ai Bing Sun School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China School of Life Science University of Science and Technology of ChinaHefei 230026China Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China University of Chinese Academy of Sciences Beijing 100049China

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 Tcells after tcr activation. During ex vivo T cell activation, the addition of excess sodium lactate(Na L) 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, Na L 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 Na L treatment group compared to the Na Cl 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.

关键词： lactate glycolysis tcr activation immunometabolism

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