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

Area of Science:

• Immunology
• Oral Pathology
• Microenvironment Research

Background:

• The adaptive immunity priming mechanism in oral mucositis is not fully understood.
• Oral lichen planus (OLP) pathogenesis requires further elucidation, particularly regarding inducible tertiary lymphoid structures (iTLSs) and stromal-immune interactions.

Purpose of the Study:

• To investigate the mechanisms of OLP, focusing on the role of iTLSs and stromal-immune microenvironments.
• To characterize the cellular composition and transcriptional signature of iTLSs in OLP.
• To determine if iTLSs influence OLP disease severity.

Main Methods:

• Single-cell RNA sequencing was used to analyze iTLSs in OLP.
• Multiplex immunofluorescence staining characterized spatial features of iTLSs.
• Retrospective clinical data from OLP patients were collected to assess the correlation between iTLSs and disease severity.

Main Results:

• Distinct cellular compositions and fibroblast-immune cell interactions were identified within OLP iTLSs.
• CCL19+ fibroblasts were found to be critical for T-cell chemotaxis, promoting iTLS development, activated by lymphotoxin.
• A significant correlation was observed between the presence of iTLSs and increased OLP severity, including atrophic-erosive forms and higher disease scores.

Conclusions:

• Fibroblast-immune cell interactions within iTLSs are key factors in OLP's inflammatory milieu.
• iTLSs are proposed as the priming structure for T-cell immunity in the oral mucosa.
• Understanding these mechanisms offers insights into OLP pathogenesis and potential therapeutic targets.