Departments of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
Sci Rep. 2016 Jul 7;6:29186. doi: 10.1038/srep29186.
Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3(+), CD4(+), and CD8(+) cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis-associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP.
口腔扁平苔藓(OLP)是一种病因不明的慢性 T 细胞介导的黏膜疾病。虽然已经考虑了各种抗原,但实际上触发 T 细胞炎症反应的原因尚不清楚。在本研究中,我们提出组织内存在的内源性细菌触发 T 细胞浸润并提供靶抗原。使用针对细菌 16S rRNA 基因的通用探针对 OLP(n=36)和正常(n=10)口腔黏膜组织进行原位杂交,并使用抗 CD3、抗 CD4、抗 CD8 和抗巨噬细胞特异性抗体进行免疫组织化学染色。细菌在 OLP 组织的整个上皮和固有层中大量存在,与浸润的 CD3(+)、CD4(+)和 CD8(+)细胞水平呈正相关。此外,在浸润的 T 细胞内也检测到了细菌。对 OLP 患者(n=13)和对照组(n=11)的黏膜微生物组进行焦磷酸测序分析显示,OLP 病变中链球菌减少,与牙龈炎/牙周炎相关的细菌增加。使用选定的细菌物种,我们证明某些口腔细菌破坏上皮物理屏障,被内化到上皮细胞或 T 细胞中,并诱导 T 细胞趋化因子 CXCL10 和 CCL5 的产生。我们的研究结果为 OLP 的发病机制提供了新的见解。