Aberrant Activation of the STING-TBK1 Pathway in γδ T Cells Regulates Immune Responses in Oral Lichen Planus

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disease. Interferon (IFN)-? has been suggested to be vital for the OLP immune responses. A prominent innate-like lymphocyte subset, ?d T cells, span the innate-adaptive continuum and exert immune effector functions by producing a wide spectrum of cytokines, including IFN-?. The involvement and mechanisms of ?d T cells in the pathogenesis of OLP remain obscure. The expression of ?d T cells in lesion tissues and in the peripheral blood of OLP patients was determined via flow cytometry and immunohistochemistry, respectively. Human leukocyte antigen-DR (HLA-DR), cluster of differentiation (CD) 69, Toll-like receptors (TLRs), natural killer group 2, member D (NKG2D) and IFN-? were detected in ?d T cells of OLP patients using flow cytometry. Additionally, the involvement of stimulator of the interferon genes (STING)-TANK-binding kinase 1 (TBK1) pathway in ?d T cells was evaluated by multi-color immunofluorescence. Western blotting was employed to investigate the regulatory mechanisms of ?d T cells in OLP. ?d T cells were significantly upregulated in the lesion tissues, whereas their peripheral counterparts were downregulated in OLP patients. Meanwhile, increased frequencies of local CD69(+) and NKG2D(+) ?d T cells and peripheral HLA-DR+ and TLR4(+) ?d T cells were detected in OLP. Furthermore, significant co-localization of STING and TBK1 was observed in the ?d T cells of OLP lesions. In addition, enhanced IFN-? and interleukin (IL)-17A were positively associated with the activated STING-TBK1 pathway and ?d T cells in OLP. Taken together, the upregulated STING-TBK1 pathway in activated ?d T cells might participate in the regulation of immune responses in OLP.