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

Abstract

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disease. Interferon (IFN)-γ has been suggested to be vital for the OLP immune responses. A prominent innate-like lymphocyte subset, γδ T cells, span the innate–adaptive continuum and exert immune effector functions by producing a wide spectrum of cytokines, including IFN-γ. The involvement and mechanisms of γδ T cells in the pathogenesis of OLP remain obscure. The expression of γδ 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-γ were detected in γδ 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 γδ T cells was evaluated by multi-color immunofluorescence. Western blotting was employed to investigate the regulatory mechanisms of γδ T cells in OLP. γδ 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+ γδ T cells and peripheral HLA-DR+ and TLR4+ γδ T cells were detected in OLP. Furthermore, significant co-localization of STING and TBK1 was observed in the γδ T cells of OLP lesions. In addition, enhanced IFN-γ and interleukin (IL)-17A were positively associated with the activated STING-TBK1 pathway and γδ T cells in OLP. Taken together, the upregulated STING-TBK1 pathway in activated γδ T cells might participate in the regulation of immune responses in OLP.

Keywords

• oral lichen planus
• γδ T cells
• STING-TBK1 pathway
• interferon-γ