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2-Deoxy-D-glucose impedes T cell-induced apoptosis of keratinocytes in oral lichen planus.

ABSTRACT: 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.

SUBMITTER: Wang F

PROVIDER: S-EPMC8572795 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Down-regulation of miRNA-27b-3p suppresses keratinocytes apoptosis in oral lichen planus.

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