Protective role of interleukin-37 in oral lichen planus: Regulation of Jurkat cell glycolysis through the mTOR pathway

Objectives: Oral Lichen planus (OLP), a potential malignant disease of the oral mucosa, is a chronically inflamed condition that impacts the quality of life of patients. Interleukin-37 (IL-37) is a potent innate and acquired immunosuppressive factor in autoimmune diseases, but its specific role in OLP remains unclear. The aim of the present study was to demonstrate the anti-inflammatory role of IL-37 in OLP.

Materials and methods: Tissue, plasma, and saliva samples were collected from patients with OLP. Immunohistochemical (IHC) staining was performed on tissue sections for histological analysis. Expression levels of IL-37 in plasma and saliva were quantified using enzyme-linked immunosorbent assay (ELISA). Jurkat cells were given a human recombinant IL-37 protein pretreatment and analysed for their ability to proliferate. Through the use of RT-qPCR and immunofluorescence, the expression of glycolytic mammalian target of rapamycin (mTOR) -related genes and proteins in T cells was identified. The migration rate of HOK cells was measured in the co-culture system using the wound healing test, and the T cell Apoptosis rate was determined using flow cytometry.

Results: [1] ELISA analysis revealed no significant differences in salivary IL-37 levels between groups; however, plasma IL-37 levels were significantly elevated in OLP patients compared with controls (p< 0.05). IHC staining of tissue samples from OLP patients revealed that IL-37 was down-regulated in the epithelial layer. [2] The effect of IL-37 on T cells alone could promote cell proliferation in the resting state and inhibit cell proliferation in the activated state, both of which could be reversed by MHY 1485, with statistically significant differences(P< 0.05). Immunofluorescence showed that mTOR phosphorylation and Lactate Dehydrogenase A (LDHA) expression were down-regulated in the activated T cells by IL-37, with statistically significant differences(P< 0.05). The results of the lactate assay suggested that IL-37 caused a decrease in total LDH release and down-regulation of glycolysis levels in T cells. [3] In the in vitro co-culture, flow cytometry results suggested that IL-37 up-regulated the Apoptosis level of activated T cells, and cell scratch assay showed that IL-37 increased the migration level of HOK cells and the difference was statistically significant(P< 0.05).

Conclusions: IL-37 was abnormally expressed in OLP and inhibited the activities of mTOR and LDHA in Jurkat cells, thereby inhibiting the conversion of pyruvate to lactate, the last link in aerobic glycolysis. IL-37 showed inhibition of the proliferative activation capacity of Jurkat cells in the co-culture system as well as increased cell viability in HOK, suggesting that IL-37 may play a protective role in OLP.

Glycolysis; Interleukin-37; Lactate dehydrogenase A; Mammalian target of rapamycin; Oral lichen planus.