Revealing the roles of IL-7R in abdominal aortic aneurysm through integrated analysis of single-cell RNA-seq and bulk RNA-seq

Abstract

Abdominal aortic aneurysm (AAA) is a common cardiovascular disease in the elderly, but there are still no therapeutic targets for this disease. In this study, we collected and analyzed bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data of AAA from the Gene Expression Omnibus (GEO) database. The immune infiltration-related genes were identified and categorized into various cell types, revealing potential key genes and pathways. Examination of three bulk RNA-seq datasets revealed a total of 4087 differentially expressed genes. The expression levels of the immune-related genes IL-7R were significantly elevated in AAA tissues across all three datasets. Furthermore, scRNA-Seq analysis revealed increased expression of IL-7R in CD4⁺ memory cells within AAA tissues. Immunofluorescence staining corroborated these findings, demonstrating increased expression of IL-7R in CD4⁺ T cells in AAA tissues. In vitro, activation of IL-7R elevated the activation of JAK/STAT pathway and phenotypic switching in SMCs, while inhibition of IL-7R abolished these effects and suppressed the secretion of IFN-γ. In conclusion, the activation of IL-7R in CD4⁺ T cells is a key contributor to the pathogenesis of AAA, as it can promote secretion of IFN-γ via JAK/STAT pathway and induce phenotypic switching of SMCs.

Keywords: Abdominal aortic aneurysm; IL-7R; Immune infiltration; RNA sequencing; Single-cell RNA sequencing.