Oral lichen planus (OLP) is a T cell–mediated immunoinflammatory disease. Glycolysis plays an essential role in T-cell immune responses. Blocking glycolytic pathway in activated T cells represents a therapeutic strategy for restraint of immunologic process in autoimmune disorders. 2-Deoxy-D-glucose (2-DG) has been widely used to probe into glycolysis in immune cells. This study was aimed to explore the role of glycolysis inhibition by 2-DG on regulating immune responses of OLP-derived T cells. We observed that lactic dehydrogenase A (LDHA) expression was elevated in OLP lesions and local T cells. 2-DG inhibited the expression of LDHA, p-mTOR, Hif1α and PLD2 in T cells; meanwhile, it decreased proliferation and increased apoptosis of T cells. T cells treated by 2-DG showed lower LDHA expression and elevated apoptosis, resulting in a reduced apoptotic population of keratinocytes that were co-cultured with them, which was related to the decreased levels of IFN-γ in co-culture system. Rapamycin enhanced the effects of 2-DG on immune responses between T cells and keratinocytes. Thus, these findings indicated that OLP-derived T cells might be highly dependent upon high glycolysis for proliferation, and 2-DG treatment combined with rapamycin might be an option to alleviate T-cell responses, contributing to reducing apoptosis of keratinocytes.

中文翻译：

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2-脱氧-D-葡萄糖阻碍 T 细胞诱导的口腔扁平苔藓角质形成细胞凋亡

口腔扁平苔藓 (OLP) 是一种 T 细胞介导的免疫炎症性疾病。糖酵解在 T 细胞免疫反应中起重要作用。阻断活化 T 细胞中的糖酵解途径代表了一种在自身免疫性疾病中抑制免疫过程的治疗策略。2-脱氧-D-葡萄糖 (2-DG) 已广泛用于探测免疫细胞中的糖酵解。本研究旨在探讨 2-DG 抑制糖酵解对调节 OLP 衍生 T 细胞免疫反应的作用。我们观察到乳酸脱氢酶 A (LDHA) 表达在 OLP 病变和局部 T 细胞中升高。2-DG抑制T细胞中LDHA、p-mTOR、Hif1α和PLD2的表达；同时，它减少了T细胞的增殖，增加了细胞凋亡。2-DG 处理的 T 细胞表现出较低的 LDHA 表达和升高的细胞凋亡，导致与它们共培养的角质形成细胞的凋亡群体减少，这与共培养系统中IFN-γ水平的降低有关。雷帕霉素增强了 2-DG 对 T 细胞和角质形成细胞之间免疫反应的影响。因此，这些发现表明，OLP 衍生的 T 细胞可能高度依赖于高糖酵解的增殖，而 2-DG 治疗与雷帕霉素联合可能是减轻 T 细胞反应的一种选择，有助于减少角质形成细胞的凋亡。