Department of Oral Medicine, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing 210029, Jiangsu, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210029, Jiangsu, China.
Department of Oral Medicine, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing 210029, Jiangsu, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210029, Jiangsu, China.
Int Immunopharmacol. 2023 Jun;119:110175. doi: 10.1016/j.intimp.2023.110175. Epub 2023 Apr 13.
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.
口腔扁平苔藓（OLP）是一种 T 细胞介导的免疫炎症性疾病。多项研究提出，大肠杆菌（E. coli）可能参与 OLP 的进展。本研究通过 Toll 样受体 4（TLR4）/核因子-kappab（NF-κB）信号通路，研究了 E. coli 及其上清液在调节 OLP 免疫微环境中 Th17/调节性 T（Treg）平衡及相关细胞因子和趋化因子谱中的功能作用。我们发现，E. coli 和上清液可激活人口腔角质细胞（HOK）和 OLP 源性 T 细胞中的 TLR4/NF-κB 信号通路，增加白细胞介素（IL）-6、IL-17、C-C 基序趋化因子配体（CCL）17 和 CCL20 的表达，从而增加维甲酸相关孤儿受体（RoRγt）的表达和 Th17 细胞的比例。此外，共培养实验表明，用 E. coli 和上清液处理的 HOK 可增加 T 细胞增殖和迁移，促进 HOK 细胞凋亡。TLR4 抑制剂（TAK-242）成功逆转了 E. coli 和其上清液的作用。因此，E. coli 和上清液激活了 HOK 和 OLP 源性 T 细胞中的 TLR4/NF-κB 信号通路，导致 OLP 中细胞因子和趋化因子表达增加及 Th17/Treg 失衡。
