1621 Spatial mass cytometry-based single cell imaging reveals a disrupted epithelial-immune axis in prurigo nodularis

Prurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by intensely pruritic, hyperkeratotic nodules that disproportionately affects Black patients. Little known about the interaction of innate immune cells with epithelial and stromal elements in PN. Thus, we utilize imaging mass cytometry (IMC) to examine cutaneous lymphocytic myeloid cell populations lesional PN skin, at single level. We prospectively collected total 28 nonlesional biopsies from healthy control patients employed IMC visualize inflammation architecture through an unbiased machine learning approach. Results revealed increased expression CD14 (P<0.01), CD3 (P<0.05), caspase 3 NFkB pSTAT3 (P<0.05) as compared controls. Keratinocytes (KCs) were clustered into distinct subpopulations CD14+CD33+, CD11c+, CD63+, 3+ KCs, CD14+ (p<0.01) KCs CD14+CD33+ decreased CAS3+CD33+ macrophage expressing pERK1/2 correlated positively patient-reported itch intensity (P=0.006). Hierarchical clustering also cluster greater history atopy NFkB+pSTAT3+pERK1/2+ monocyte-derived dendritic (MoDCs), vimentin (P<0.05). Neighborhood analysis found significant interactions between macrophages, CD3+ T cells, MoDCs, markers. These findings suggest disrupted epithelial-immune axis underlies pathogenesis.