Characterizing inducible tertiary lymphoid structures in oral lichen planus: implications for stromal-immune cells interaction and disease severity

Stromal-immune cells interaction and their contribution in the pathogenesis of oral mucositis, remained not fully understood. This made it hard to clarify the underlying mechanism linking systemic immunity and regional immune microenvironment. The present study aims to elucidate the underpinnings of oral lichen planus (OLP) by focusing on the role of inducible tertiary lymphoid structures (iTLSs) and their impact on disease progression. Employing single-cell RNA sequencing and multiple immunofluorescences, we identified distinct cellular compositions and stromal-immune cells interactions within the iTLSs of OLP. We particularly highlighted the role of CCL19 ⁺ fibroblasts and HEV cells. These stromal cells might play a crucial role in facilitating lymphocytes trafficking from peripheral blood to the local inflammation sites within oral mucosa, thereby promoting the formation of iTLSs in OLP. Our findings also revealed a significant correlation between the presence of iTLSs and increased severity of OLP, marked by more atrophic-erosive forms and higher REU scores in patients with iTLSs. The present research offered new insights into the pathogenic mechanisms of OLP, proposing the stromal-immune cell interactions within iTLSs as essential factors in the disease's inflammatory milieu. These findings contributed to uncovering the specific regional pathological features in OLP. Hence, the characterization of iTLSs provided a fundamental foundation for further studies in oral mucosal immunity.