Kim Yu Gyung, Song Hyo-Jin, Kim Hyeon Ji, Joo Bo Kyung, Cho Jin-Hwa, Jung Won, Jang Sungil, Choi Song-Yi, Lee Heon-Jin, Byun Jin-Seok, Kim Do-Yeon
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea.
Department of Oral Medicine, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University, Jeonju, 54907, Republic of Korea.
Inflammation. 2024 Sep 21. doi: 10.1007/s10753-024-02146-8.
Oral lichen planus (OLP) is a chronic inflammatory disease characterized by an intensive infiltration of cytotoxic T cells, which causes keratinocyte death. Abnormal changes within keratinocytes might be critical for OLP onset and progression, but the pathogenic mechanism of OLP is still uncertain. The human oral microbiota, consisting of approximately 50-100 billion bacterial entities, encompasses around 200 dominant bacterial species. These bacteria continuously produce and release extracellular vesicles (EVs), which play a significant role in host-microbe interactions. However, the impact of these bacterial EVs on the progression of OLP has not been fully elucidated. In this study, through comprehensive database analysis and experimental validation, we observed that OLP lesions exhibit elevated inflammatory signatures and significantly increased phosphorylation of STAT3 compared to non-OLP tissues. Notably, EVs derived from key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were shown to induce an inflammatory response and activate STAT3 signaling pathways, closely mirroring the pathophysiological features observed in OLP. These results underscore the potential role of bacterial EVs in the pathogenesis of OLP and highlight STAT3 as a critical mediator in this process.
口腔扁平苔藓(OLP)是一种慢性炎症性疾病,其特征是细胞毒性T细胞大量浸润,导致角质形成细胞死亡。角质形成细胞内的异常变化可能对OLP的发生和发展至关重要,但OLP的致病机制仍不确定。人类口腔微生物群由约5000亿至10000亿个细菌个体组成,包含约200种优势细菌。这些细菌持续产生并释放细胞外囊泡(EVs),其在宿主-微生物相互作用中发挥重要作用。然而,这些细菌来源的EVs对OLP进展的影响尚未完全阐明。在本研究中,通过全面的数据库分析和实验验证,我们观察到与非OLP组织相比,OLP病变表现出炎症特征升高,且STAT3的磷酸化显著增加。值得注意的是,来自关键牙周病原体牙龈卟啉单胞菌和伴放线聚集杆菌的EVs被证明可诱导炎症反应并激活STAT3信号通路,这与OLP中观察到的病理生理特征极为相似。这些结果强调了细菌EVs在OLP发病机制中的潜在作用,并突出了STAT3作为这一过程中的关键介质。