Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon, Republic of Korea.
PLoS One. 2021 Sep 10;16(9):e0257356. doi: 10.1371/journal.pone.0257356. eCollection 2021.
Oral lichen planus (OLP) is one of the most prevalent oral mucosal diseases, but there is no cure for OLP yet. The aim of this study was to gain insights into the role of barrier dysfunction and infection in OLP pathogenesis through analysis of transcriptome datasets available in public databases. Two transcriptome datasets were downloaded from the Gene Expression Omnibus database and analyzed as whole and as partial sets after removing outliers. Differentially expressed genes (DEGs) upregulated in the dataset of OLP versus healthy epithelium were significantly enriched in epidermal development, keratinocyte differentiation, keratinization, responses to bacterial infection, and innate immune response. In contrast, the upregulated DEGs in the dataset of the mucosa predominantly reflected chemotaxis of immune cells and inflammatory/immune responses. Forty-three DEGs overlapping in the two datasets were identified after removing outliers from each dataset. The overlapping DEGs included genes associated with hyperkeratosis (upregulated LCE3E and TMEM45A), wound healing (upregulated KRT17, IL36G, TNC, and TGFBI), barrier defects (downregulated FRAS1 and BCL11A), and response to infection (upregulated IL36G, ADAP2, DFNA5, RFTN1, LITAF, and TMEM173). Immunohistochemical examination of IL-36γ, a protein encoded by one of the DEGs IL36G, in control (n = 7) and OLP (n = 25) tissues confirmed the increased expression of IL-36γ in OLP. Collectively, we identified gene signatures associated with hyperkeratosis, wound healing, barrier defects, and response to infection in OLP. IL-36γ, a cytokine involved in both wound repair and antimicrobial defense, may be a possible therapeutic target in OLP.
口腔扁平苔藓（OLP）是最常见的口腔黏膜疾病之一，但目前尚无治疗 OLP 的方法。本研究旨在通过分析公共数据库中可用的转录组数据集，深入了解屏障功能障碍和感染在 OLP 发病机制中的作用。从基因表达综合数据库中下载了两个转录组数据集，并在去除离群值后作为整体和部分数据集进行分析。与健康上皮相比，OLP 数据集上调的差异表达基因（DEG）在表皮发育、角蛋白细胞分化、角化、对细菌感染的反应和先天免疫反应中显著富集。相比之下，黏膜数据集上调的 DEG 主要反映了免疫细胞的趋化作用和炎症/免疫反应。在从每个数据集去除离群值后，从两个数据集中识别出 43 个重叠的 DEG。重叠的 DEG 包括与过度角化（上调 LCE3E 和 TMEM45A）、伤口愈合（上调 KRT17、IL36G、TNC 和 TGFBI）、屏障缺陷（下调 FRAS1 和 BCL11A）和感染反应（上调 IL36G、ADAP2、DFNA5、RFTN1、LITAF 和 TMEM173）相关的基因。对其中一个 DEG IL36G 编码的蛋白质 IL-36γ在对照（n=7）和 OLP（n=25）组织中的免疫组织化学检查证实了 OLP 中 IL-36γ 的表达增加。综上所述，我们确定了与 OLP 中过度角化、伤口愈合、屏障缺陷和感染反应相关的基因特征。IL-36γ，一种参与伤口修复和抗菌防御的细胞因子，可能是 OLP 的一个潜在治疗靶点。
