346 Transcriptomes of CD27-CD28- and CD27+CD28+ CD8+ T subsets disclose differentially expressed novel genes and signaling pathways in Behçet’s disease

Abstract

Immunosenescence is related to increased susceptibility to infectious diseases, vaccine failure, and chronic low-grade systemic inflammation, such as Behçet’s disease (BD). Our previous study has shown an increased frequency of senescent CD8+ T cells in the peripheral blood of BD patients. To find the global gene-expression characteristics of senescent CD8+ T cells in relation with BD, we examined the transcriptome of CD8+ T lymphocyte subsets (CD27+CD28+ nonsenescent and CD27-CD28- senescent) from BD patients and healthy control subjects (HC). We recruited 18 BD patients and 18 HC for RNA-sequencing and 5 BD patients and 5 HC for validation of RNA-sequencing. Differentially expressed 1103 genes were identified in BD CD27-CD28- subsets compared to HC, while 652 genes were differentially expressed in BD CD27+CD28+ subsets compared to HC. PCR was conducted for the validation of RNA-sequencing and as a result, COL5A1, ARHGEF10, and LOC102724428 in BD CD27-CD28- subsets compared to HC showed a tendency to match RNA-sequencing. Among them, COL5A1 showed statistical significance. Meanwhile, the BD CD27+CD28+ subsets compared to HC showed the same tendency as RNA-sequencing in TRPV3, ARHGEF10, UBE2F-SCLY, CD302, SHANK1, and the statistical significance was found in TRPV3 and ARHGEF10. Of the significant canonical pathways identified in IPA, 11 pathways tended to be opposite in CD27+CD28+ and CD27-CD28- subsets, while two pathways showed activity in the same direction. The most significant canonical pathway resulted from the IPA was the “cAMP-mediated signaling”. This is the first study for transcriptome analysis of CD8+ T cells of BD patients compared to HCs. Using these DEGs may be useful for developing biomarkers in BD and help to make diagnosis easier. Also, we hope that this genetic profiling can be used as a key for approaching the pathogenesis of BD.