Immune mechanisms driving clinical heterogeneity in oral lichen planus

Oral lichen planus (OLP) is a clinically localized mucosal disease that nonetheless exhibits systemic immune alterations contributing to its heterogeneous presentations. This study investigated systemic immunological profiles associated with reticular (ROLP) and erosive (EOLP) OLP by analyzing circulating lymphocyte subsets and PBMC-derived cytokine secretion. Peripheral blood mononuclear cells from 91 participants (30 controls, 31 ROLP, 30 EOLP) were assessed by 24-colour spectral flow cytometry, and cytokine production was measured following CD3/CD28 stimulation. ROLP patients showed significantly elevated IL-2, IL-4, IL-17 A, and TNF-α secretion, whereas both OLP subgroups exhibited increased TGF-β1 compared with controls. Flow cytometry revealed higher frequencies of CD4⁺ Th1 cells in ROLP and increased naïve B-cell proportions in both ROLP and EOLP. Both clinical forms displayed enhanced TIGIT expression across CD4⁺, CD8⁺, and NK cells. These findings indicate distinct systemic immune signatures: a Th1/Th17-associated cytokine-driven inflammatory profile in ROLP and an inhibitory immune profile characterized by persistent TGF-β1 elevation in EOLP. Together, these data support the contribution of systemic immune dysregulation to OLP heterogeneity and highlight immunoregulatory pathways that warrant further investigation.