Spatial proteomics of immune checkpoints in discoid lupus and lichen planus

Summary: Interface dermatoses a histopathological pattern observed in several autoimmune connective tissue diseases, including discoid lupus erythematosus (DLE) and lichen planus (LP). Despite distinct clinical presentations, both diseases share histologic features suggestive of common underlying pathogenic mechanisms. However, their immunoregulatory landscapes remain unclear. This study employs spatial proteomics to characterize immune inhibitory receptor expression in DLE and LP, revealing disease-specific and overlapping immune checkpoint pathways. We analyzed archival DLE and LP skin biopsies using the NanoString GeoMx Immuno-Oncology protein panel. Heatmap and UMAP clustering demonstrated distinct protein expression profiles between DLE and LP. Cross-segmentation analysis of keratinocytes (PanCK+), CD4+, and CD8+ T cells identified differential immune checkpoint and T cell activation expression. In DLE, immune modulation was compartmentalized, with keratinocytes expressing PD-L2, CD44, and CD127 compared to CD4+ and CD8 T cells. Additionally, CD4+T cells in DLE expressed greater ICOS, CTLA4, OX40L, CD40, 4-1BB, and PD-1 compared to CD8+ T cells. In contrast to DLE, CD4+ and CD8+ T cells within LP tissues expressed VISTA, PD-L1, and STING, whereas keratinocytes express OX40L, CD127, CD44 and ARG1. These findings underscore key immunoregulatory differences in interface dermatoses and suggest potential therapeutic strategies, including immune checkpoint agonists, for targeted intervention in autoimmune dermatoses Ummugulsum Yildiz Altay¹, Rachel Breidbart¹, Michal Kidacki¹, Anjali Jaiswal¹, Christina Cho², Matthew D. Vesely¹ 1. Dermatology, Yale School of Medicine, New Haven, CT, United States. 2. Immunobiology, Yale School of Medicine, New Haven, CT, United States. Adaptive and Auto-Immunity