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The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus.
Immunobiology ( IF 2.5 ) Pub Date : 2020-03-09 , DOI: 10.1016/j.imbio.2020.151933
Fang Wang 1 , Jing Zhang 2 , Gang Zhou 2
Affiliation  

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.



中文翻译:

mTOR-糖酵解途径促进口腔扁平苔藓中的 T 细胞免疫生物学。

口腔扁平苔藓 (OLP) 是一种 T 细胞介导的炎症性黏膜疾病。T 细胞在被免疫刺激激活后需要对其效应功能进行快速代谢重编程。哺乳动物雷帕霉素靶蛋白 (mTOR) 是 T 细胞代谢重编程和免疫反应的核心参与者。本研究调查了 mTOR 在 OLP 免疫代谢中的作用。mTOR 及其直接靶标真核起始因子 4E 结合蛋白 1 (4E-BP1) 在 OLP 患者的外周 T 细胞中高度磷酸化。雷帕霉素介导的 mTOR 激活阻断抑制了 T 细胞增殖和 DNA 合成,促进了细胞凋亡,并降低了 Th1/Th2 和 Th17/Treg 比率。与单独选择性抑制 PI3K 相比,mTOR 和磷脂酰肌醇 3-激酶 (PI3K) 的双重阻断对 T 细胞免疫生物学的抑制作用更强。雷帕霉素还阻断了 T 细胞中的糖酵解途径。此外,葡萄糖诱导的 mTOR-糖酵解途径激活增加了 T 细胞增殖、DNA 合成和 Th17/Treg 比率,并减少了 T 细胞凋亡。相反,2-脱氧-d-葡萄糖 (2-DG) 通过阻断 mTOR 通路对 T 细胞免疫生物学产生相反的影响。总之,mTOR-糖酵解途径的增强激活促进了 T 细胞免疫生物学,表明免疫代谢失调可能与 OLP 中的 T 细胞功能障碍有关。

更新日期:2020-04-21
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