The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus

Fang Wang, Jing Zhang, Gang Zhou
Immunobiology 2020 March 9, : 151933
Oral lichen planus (OLP) is a T-cell-mediated inflammatory mucosal disease. T cells require rapid metabolic reprogramming for their effector functions after activation by immunologic stimuli. The mammalian target of rapamycin (mTOR) is a central player in the metabolic reprogramming and immune responses of T cells. The present study investigated the role of mTOR in the immunometabolism of OLP. mTOR and its direct target eukaryotic initiation factor 4E binding protein 1 (4E-BP1) were highly phosphorylated in peripheral T cells of OLP patients. Rapamycin-mediated blockage of mTOR activation restrained both T-cell proliferation and DNA synthesis, promoted apoptosis, and decreased Th1/Th2 and Th17/Treg ratios. Dual blockage of mTOR and phosphatidylinositol 3-kinase (PI3K) exerted stronger inhibition on T-cell immunobiology than selective repression of PI3K alone. Rapamycin also blocked the glycolytic pathway in T cells. Moreover, glucose-induced activation of mTOR-glycolytic pathway increased T-cell proliferation, DNA synthesis, and the Th17/Treg ratio, and decreased T-cell apoptosis. In contrast, inhibition of glycolysis by 2-Deoxy-d-glucose (2-DG) yielded the opposite effects on T-cell immunobiology by blocking the mTOR pathway. In conclusion, enhanced activation of the mTOR-glycolytic pathway promoted T-cell immunobiology, suggesting that dysregulation of immunometabolism might be associated with T-cell dysfunction in OLP.

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