Transcriptional analysis of neutrophils from patients with Behçet's disease reveals activation and chemotaxis of neutrophils.

ABSTRACT

Behçet's disease (BD) is a systemic vasculitis characterized by neutrophil activation with unclear pathogenesis. This study aimed to explore the transcriptional profiles of BD neutrophils and identify specific gene signatures. We performed RNA sequencing on neutrophils from treatment-naive active BD patients and healthy controls, then analyzed differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) and transcription regulatory network. Quantitative real-time PCR and Western Blot were used to validate chemotaxis-related DEGs expression. We detected 567 DEGs, including 520 upregulated genes and 47 downregulated genes. 9 KEGG pathways were enriched, dominated by the NF-κB pathway and chemotaxis. The transcription regulatory network suggests ETS1 regulated the enhanced chemotaxis of BD neutrophils. Validation experiments demonstrated the overexpression of ETS1, CCR6 and CCL5 in BD neutrophils compared with HC, and ETS1 was significantly increased in vascular BD compared with other BD subgroups. Our study revealed increased activation and chemotaxis of BD neutrophils characterized by the overexpression of CCL5, CCR6 and ETS1.