Single-Cell Profiling of Lichen Planus Reveals Type I IFN Response Triggering the Interface Dermatitis Reaction

Cutaneous lichen planus (LP) is an inflammatory skin disease characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte (KC) cell death. The aim of this study was to investigate the immunopathogenesis of LP and assess the underlying mechanisms that drive the interface dermatitis reaction. We first performed single-cell RNA sequencing on lesional skins from patients with LP compared with healthy control skins and demonstrate that LP skin is imprinted by a type I IFN-rich environment. We highlight unique subsets of inflammatory KCs and fibroblasts highly influenced by type I IFN. We then performed interactome analyses, revealing a close communication between IFN-imbued KCs and immune skin cells. Subsequently, to assess the functional effect of IFN subtypes on the interaction between KCs and CD8⁺ T cells, we performed in vitro models of interface dermatitis. We show that IFN-b sensibilizes KCs to CD8⁺ T-cell-mediated cell death in both allogenic and autologous coculture models. In this study, we illustrate that type I IFN education on skin cells drives the interface dermatitis reaction, thus orchestrating the cross-talk between immune and resident cells in LP skin. Together, our data provide a comprehensive characterization of LP immunopathogenesis and demonstrate the strong involvement of type I IFN in its inflammatory landscape.