Single-cell and molecular insights into the immunopathogenic mechanisms of oral mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is a chronic autoimmune bullous disorder, characterized pathologically by subepidermal blistering inflammation primarily affecting mucosal surfaces. The immunopathogenesis of MMP involves a complex interplay between cytokines, epithelial components, and immune cells, yet the specific cell subsets driving disease progression, especially in oral mucosal lesions, remain poorly defined. To address this gap in knowledge, we performed integrated single-cell transcriptomic and immune repertoire profiling of paired oral mucosal lesions and peripheral blood samples from MMP patients prior to therapeutic intervention. Our analyses uncover a multifaceted pathogenic signature, including aberrant WNT4 signaling, dysfunctional Th17 cell responses, TNF-α-producing macrophages, expanded T cell clones enriched in the TRBV20-1 gene segment, and dysregulated fibroblast subsets. Collectively, these findings provide new insights into the key immunopathogenic mechanisms underlying MMP and establish a molecular framework for the development of targeted immunotherapies for this condition.