1 Université Côte d'Azur, EA 7354 MICORALIS, UFR Odontologie, Nice, France.
2 Centre Hospitalier Universitaire de Nice, Pôle Odontologie, Nice, France.
J Dent Res. 2018 Dec;97(13):1494-1500. doi: 10.1177/0022034518788282. Epub 2018 Jul 13.
Epstein-Barr virus (EBV), in addition to its transforming properties, contributes to the pathogenesis of several inflammatory diseases. Here, we investigated its involvement in oral lichen planus (OLP), a common autoimmune-like disease of unknown etiopathogenesis that can display a malignant potential. EBV-infected cells (EBV+ cells) were sought in a large series of clinically representative OLPs ( n = 99) through in situ hybridization to detect small noncoding EBV-encoded RNAs. Overall, our results demonstrated that EBV was commonly found in OLP (74%), with significantly higher frequency (83%) in the erosive form than in the reticular/keratinized type mild form (58%). Strikingly, many erosive OLPs were massively infiltrated by large numbers of EBV+ cells, which could represent a large part of the inflammatory infiltrate. Moreover, the number of EBV+ cells in each OLP section significantly correlated with local inflammatory parameters (OLP activity, infiltrate depth, infiltrate density), suggesting a direct relationship between EBV infection and inflammatory status. Finally, we characterized the nature of the infiltrated EBV+ cells by performing detailed immunohistochemistry profiles ( n = 21). Surprisingly, nearly all EBV+ cells detected in OLP lesions were CD138+ plasma cells (PCs) and more rarely CD20+ B cells. The presence of EBV+ PCs in erosive OLP was associated with profound changes in cytokine expression profile; notably, the expression of key inflammatory factors, such as IL1-β and IL8, were specifically increased in OLP heavily infiltrated with EBV+ PCs. Moreover, electron microscopy-based experiments showed that EBV+ PCs actively produced EBV viral particles, suggesting possible amplification of EBV infection within the lesion. Our study thus brings conclusive evidence showing that OLP is commonly infiltrated with EBV+ PCs, adding a further puzzling element to OLP pathogenesis, given that PCs are now considered to be major regulatory immune cells involved in several autoimmune diseases (ClinicalTrials.gov NCT02276573).
EB 病毒（EBV）除了具有转化特性外，还参与了几种炎症性疾病的发病机制。在这里，我们研究了它在口腔扁平苔藓（OLP）中的作用，OLP 是一种常见的自身免疫样疾病，其病因不明，但具有恶性潜能。通过原位杂交检测小非编码 EBV 编码 RNA，在一系列具有临床代表性的 OLP（n=99）中寻找 EBV 感染细胞（EBV+细胞）。总的来说，我们的结果表明 EBV 通常存在于 OLP 中（74%），在糜烂型中的频率明显高于网纹/角化型轻度型（58%）（83%）。引人注目的是，许多糜烂性 OLP 大量浸润了大量的 EBV+细胞，这些细胞可能代表了炎症浸润的很大一部分。此外，每个 OLP 切片中 EBV+细胞的数量与局部炎症参数（OLP 活性、浸润深度、浸润密度）显著相关，提示 EBV 感染与炎症状态之间存在直接关系。最后，我们通过详细的免疫组织化学分析（n=21）来描述浸润的 EBV+细胞的性质。令人惊讶的是，在 OLP 病变中检测到的几乎所有 EBV+细胞都是 CD138+浆细胞（PC），而 CD20+B 细胞则较少。在糜烂性 OLP 中存在 EBV+PC 与细胞因子表达谱的深刻变化有关；值得注意的是，在 EBV+PC 大量浸润的 OLP 中，关键炎症因子如 IL1-β 和 IL8 的表达明显增加。此外，基于电子显微镜的实验表明，EBV+PC 能够主动产生 EBV 病毒颗粒，提示在病变内 EBV 感染可能会扩增。因此，我们的研究提供了确凿的证据，表明 OLP 通常浸润有 EBV+PC，这为 OLP 的发病机制增添了一个令人费解的因素，因为 PC 现在被认为是参与几种自身免疫性疾病的主要调节性免疫细胞（ClinicalTrials.gov NCT02276573）。
