Single-cell profiling of lichen planus reveals type I interferon response triggering the interface dermatitis reaction.

Abstract

Cutaneous lichen planus (LP) is an inflammatory skin disease characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte 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 LP patients 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 keratinocytes and fibroblasts highly influenced by type I IFN. We then performed interactome analyses, revealing a close communication between IFN-imbued keratinocytes and immune skin cells. Subsequently, to assess the functional effect of IFN subtypes on the interaction between keratinocytes and CD8⁺ T cell, we performed in-vitro models of interface dermatitis. We show that IFN-β sensibilizes keratinocytes to CD8⁺ T cells mediated cell-death in both allogenic and autologous co-culture models. Herein, 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.