The State Key Laboratory Breeding Base of Basic Science of Stomatology (HubeiMOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Cell Mol Med. 2021 Nov;25(21):10257-10267. doi: 10.1111/jcmm.16964. Epub 2021 Oct 21.
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.
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 细胞免疫反应中起着至关重要的作用。在活化的 T 细胞中阻断糖酵解途径代表了一种用于抑制自身免疫疾病中免疫过程的治疗策略。2-脱氧-D-葡萄糖(2-DG)已被广泛用于研究免疫细胞中的糖酵解。本研究旨在探讨 2-DG 通过抑制糖酵解对调节 OLP 来源的 T 细胞免疫反应的作用。我们观察到,乳酸脱氢酶 A(LDHA)在 OLP 病变和局部 T 细胞中的表达上调。2-DG 抑制 T 细胞中 LDHA、p-mTOR、Hif1α 和 PLD2 的表达;同时,它降低 T 细胞的增殖并增加其凋亡。用 2-DG 处理的 T 细胞显示出较低的 LDHA 表达和较高的凋亡,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 水平降低有关。雷帕霉素增强了 2-DG 对 T 细胞与角质形成细胞之间免疫反应的影响。因此,这些发现表明,OLP 来源的 T 细胞可能高度依赖于高糖酵解来增殖,并且 2-DG 联合雷帕霉素治疗可能是减轻 T 细胞反应的一种选择,有助于减少角质形成细胞的凋亡。