Escherichia coli enhances Th17/Treg imbalance via TLR4/NF-κB signaling pathway in oral lichen planus

Oral lichen planus (OLP) is a T-cell-mediated immunoinflammatory disease. Several studies have proposed that Escherichia coli (E. coli) may participate in the progress of OLP. In this study, we examined the functional role of E. coli and its supernatant via Toll-like Receptor 4 (TLR4)/nuclear factor-kappab (NF-κB) signaling pathway in regulating T helper (Th) 17/ regulatory T (Treg) balance and related cytokines and chemokines profile in OLP immune microenvironment. We discovered that E. coli and supernatant could activate the TLR4/NF-κB signaling pathway in human oral keratinocytes (HOKs) and OLP-derived T cells and increase the expression of interleukin (IL)-6, IL-17, C-C motif chemokine ligand (CCL) 17 and CCL20, thereby increasing the expression of retinoic acid-related orphan receptor (RoRγt) and the proportion of Th17 cells. Furthermore, the co-culture experiment revealed that HOKs treated with E. coli and supernatant increased T cell proliferation and migration, which promoted HOKs Apoptosis. TLR4 Inhibitor (TAK-242) successfully reversed the effect of E. coli and its supernatant. Consequently, E. coli and supernatant activated the TLR4/NF-κB signaling pathway in HOKs and OLP-derived T cells, leading to increased cytokines and chemokines expression and Th17/Treg imbalance in OLP.

Chemokines; Cytokines; E. coli; Oral lichen planus; TLR4/NF-κB; Th17/Treg.