Transcriptomic analysis of low-density neutrophils (LDNs) in acute generalized pustular psoriasis (GPP)

Generalized pustular psoriasis (GPP) is a severe disease featured by neutrophilic pustules and enhanced IL-36 inflammatory pathway in skin. Recently, a transcriptomic analysis of PBMCs and neutrophils in MPO-deficient GPP patients has been performed in stable disease state. However, transcriptomic profiling of PBMCs during acute flare of GPP is unclear. Here, we reported a predominant neutrophil signature in GPP PBMC and a marked increase in the CD66+CD16+ low-density neutrophils (LDNs) within the PBMC fraction of acute GPP patients. Transcriptomic and functional analysis of LDNs revealed a hypoinflammatory phenotype yet enhanced release of neutrophil granule proteases, implicating that LDNs might contribute to the IL-36-mediated inflammation in GPP patients. Comparative gene expression profiling analysis of RNA-seq data for low-density neutrophils (LDNs) and autologous normal-density neutrophils (NDNs) from 4 generalized pustular psoriasis (GPP) patients, and NDNs from 3 healthy donors