Gene signatures associated with barrier dysfunction and infection in oral lichen planus identified by analysis of transcriptomic data

• Published in: PloS one Vol. 16; no. 9; p. e0257356
• Main Authors: Vo, Phuc Thi-Duy, Choi, Sun Shim, Park, Hae Ryoun, Lee, Ahreum, Jeong, Sung-Hee, Choi, Youngnim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.09.2021; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Antiinfectives and antibacterials; Bacterial diseases; Biology and Life Sciences; Biotechnology; Cell Differentiation - drug effects; Chemotaxis; Cluster analysis; Cytokines; Cytokines - metabolism; Datasets; Defects; Dental research; Dentistry; Diagnosis; Down-Regulation; Epithelium; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic aspects; Genetic transcription; Humans; Immune response; Immune system; Immunity, Innate - drug effects; Immunohistochemistry; Immunology; Infections; Inflammation; Innate immunity; Keratinization; Keratins - drug effects; Lichen planus; Lichen Planus, Oral - genetics; Lichen Planus, Oral - metabolism; Male; Medicine and Health Sciences; Middle Aged; Mucosa; Outliers (statistics); Pathogenesis; Principal components analysis; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - metabolism; Signatures; Skin diseases; Therapeutic targets; Transcriptome; Transcriptomes; Up-Regulation; Wound healing; Wound Healing - drug effects; South Korea; United States > US; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0257356

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.