Distinct Immunological Features Compared to Lichen Planus and Oral Lichen Planus

Lichen planus (LP) and oral lichen planus (OLP) share clinical and histological similarities, yet their distinct immunopathological mechanisms make differentiation and management challenging. Clarifying these differences is essential for accurate diagnosis and treatment. This study aimed to investigate the systemic immune profile of OLP using single-cell transcriptomics, identifying distinct immune cell subsets and signaling pathways contributing to its chronic inflammatory state. Additionally, it sought to compare the inflammatory lesion microenvironments of OLP and LP by analyzing key immune pathways and cellular interactions.

Peripheral blood mononuclear cells (PBMCs) were obtained from 16 OLP patients and 5 healthy controls. Single-cell transcriptomic data from PBMCs and lesion tissues of OLP and LP were analyzed to profile immune and inflammatory signatures. Key molecular findings were validated using independent datasets and enzyme-linked immunosorbent assays (ELISA).

Prostaglandin D2 synthase (PTGDS), a pivotal enzyme in prostaglandin metabolism, emerged as a diagnostic marker with elevated expression in NK cells from OLP patients. Additionally, a novel CXCR4 ^high-TSC22D3 ^high CD4 cytotoxic T cell subset with enhanced cytotoxicity was identified, potentially contributing to OLP pathogenesis. OLP blood samples also demonstrated significant upregulation of TNF and TLR signaling in NK cells, indicating a heightened chronic inflammatory state. Comparative tissue analysis revealed intensified TNF-driven inflammation and a disrupted HIF1A- vascular endothelial growth factor (VEGF) interactions in OLP, contrasting with LP's robust VEGF-mediated angiogenesis.

These findings highlight distinct immunopathogenic mechanisms between OLP and LP. The upregulation of PTGDS in NK cells and CXCR4 ^high-TSC22D3 ^high CD4 cytotoxic T cells in PBMCs indicates systemic immune dysregulation in OLP, while tissue-level differences suggest impaired vascular remodeling and chronic inflammation. These insights underscore the need for targeted immunomodulatory therapies.

This study identifies distinct immune signatures that differentiate OLP from LP, highlighting potential therapeutic targets that require further validation for personalized treatment strategies.