CCL19⁺ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study

Objectives: The priming mechanism of adaptive immunity in oral mucositis remains unclarified. This study aimed to elucidate the mechanisms of oral lichen planus (OLP), with a specific focus on the role of inducible tertiary lymphoid structures (iTLSs) and stromal-immune microenvironments within OLP. Materials and Methods: We employed single-cell RNA sequencing and multiplex immunofluorescence staining to characterize the spatial characteristics and transcriptional signature of iTLSs in OLP. To investigate whether the presence of iTLSs influences the disease severity of OLP, we retrospectively collected clinical data from OLP patients. Results: Based on single-cell resolution analysis, we identified distinct cellular compositions and fibroblast-immune cells interactions within the iTLSs of OLP. We highlighted the critical role of CCL19⁺ fibroblasts in T-cell chemotaxis, promoting the development of iTLSs. Lymphotoxin was demonstrated to activate fibroblasts expressing CCL19. We revealed a significant correlation between the presence of iTLSs and increased severity of OLP, marked by more atrophic-erosive forms and higher disease scores in patients with iTLSs. Conclusions: The present research proposed the fibroblast-immune cell interactions within iTLSs as essential factors in OLP's inflammatory milieu, indicating iTLSs as the priming structure of T-cell immunity in the local oral mucosa.