Th115 - Spatial Proteomic and Transcriptomic Profiling of Lichen Planus

Abstract Text: Lichen planus (LP) is a chronic autoimmune mucocutaneous disease characterized by pruritic skin lesions and painful mucosal ulcers. It is estimated to affect nearly 1 million people in the US. There are no FDA-approved therapies and current treatments are often ineffective in severe cases. To better understand the immune infiltration of lichen planus, we performed single cell spatial proteomics and spatial transcriptomics on biopsy specimens of LP with comparisons to other inflammatory skin diseases and healthy control skin. We performed multiplex ion beam imaging time-of-flight (MIBI-TOF) on archived biopsies and identified 26 unique cell populations, revealing a unique structured immune cell composition for each inflammatory skin disease. LP had the greatest number of regulatory T cells and CD8+ memory T cells. Nearest neighbor spatial analysis revealed that CD11c+ cells are the closest interacting cells with keratinocytes along the dermal epidermal junction. Next, we performed spatial transcriptomics using NanoString Digital Spatial Profiling to interrogate gene expression within CD4 T cells, CD8 T cells, and keratinocytes in a spatially resolved manner. Both T lymphocytes and keratinocytes express mixed inflammatory patterns in lichen planus. For example, keratinocytes have increased expression of type 1 interferon signaling, neuroinflammation signaling, Th1 and Th2 inflammatory pathway activation. Taken together, we have demonstrated a unique structured immune architecture in LP using both spatial proteomic and spatial transcriptomic approaches that may inform future therapeutic targets.