Differential expression of novel genes and signalling pathways of senescent CD8+ T cell subsets in Behcet's disease

Abstract

OBJECTIVES: Behcet's disease (BD) is a rare disease characterised by recurrent mucocutaneous ulceration and chronic multi-systemic inflammation; however, its pathogenic mechanisms and biomarkers have not been fully discovered. Previously, we found that peripheral blood CD8+CD27-CD28- T cell frequency was higher in patients with BD than in healthy controls (HCs). In this study, we used global gene expression analysis to identify candidate genes that might be related to pathogenesis or developed as biomarkers in two CD8+ T cell subsets from BD patients and HCs. METHODS: We performed RNA sequencing analysis in CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets isolated from 18 patients with BD and healthy controls. Real time qPCR was used to validate the differential expression of genes in five patients with BD and healthy controls. RESULTS: We found that 1,103 genes and 652 genes were differentially expressed in the CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets of patients with BD, respectively. We validated the differential expression of COL5A1 in CD8+CD27-CD28- T cells and TRPV3 and ARHGEF10 in CD8+CD27+CD28+ T cells. Furthermore, Ingenuity Pathway Analysis indicated that eleven pathways were more active in BD CD8+CD27-CD28- T cells and more suppressed in BD CD8+ CD27+CD28+ T cells than in the HCs. CONCLUSIONS: Our study is the first transcriptome analysis of CD8+ T cell subsets in patients with BD and our results provide novel genes that might be related to BD pathogenesis.