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

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Cutaneous lichen planus (LP) is an inflammatory skin condition.
• LP involves interface dermatitis, lymphocyte infiltration, and keratinocyte cell death.
• The precise immunopathogenesis of LP remains to be fully elucidated.

Purpose of the Study:

• To investigate the immunopathogenesis of cutaneous lichen planus (LP).
• To identify the mechanisms driving the interface dermatitis reaction in LP.
• To explore the role of type I interferon (IFN) in LP.

Main Methods:

• Single-cell RNA sequencing of lesional and healthy skin.
• Interactome analyses to study cell communication.
• In-vitro models of interface dermatitis using co-cultures.

Main Results:

• LP skin exhibits a type I IFN-rich environment.
• Unique subsets of keratinocytes and fibroblasts are influenced by type I IFN.
• IFN-β sensitizes keratinocytes to CD8+ T cell-mediated death.

Conclusions:

• Type I IFN signaling is central to LP immunopathogenesis.
• IFN-educated skin cells orchestrate immune and resident cell cross-talk in LP.
• This study comprehensively characterizes LP's inflammatory landscape.