Multi-omics Reveals CCL3 Driving Neuronal Sensitization in Chronic Pruritus of Unknown Origin

Chronic pruritus is a pathological condition associated with numerous systemic, dermatologic, and neurologic disorders. Chronic pruritus of unknown origin (CPUO) represents a distinct clinical subtype characterized by persistent itch without an identifiable underlying cause. While emerging evidence implicates neuroimmune dysregulation in chronic pruritus, the specific mechanisms driving CPUO remain poorly understood. Objective: To characterize the neuroimmune mechanisms underlying CPUO, with a focus on identifying potential diagnostic markers. Single-cell RNA sequencing of peripheral blood cells from patients and healthy controls was conducted. Single-cell transcriptomic analysis revealed dysregulated monocytes and hyperactive natural killer (NK) cells overexpressing CCL3. Overall design: RNA-seq profiling of peripheral blood cells from 4 CPUO patients and 4 matched healthy controls