Identification of key genes and pathways contributing to artery tertiary lymphoid organ development in advanced mouse atherosclerosis

Atherosclerosis is a leading cause of mortality worldwide. Artery tertiary lymphoid organ (ATLO) neogenesis is affected by abdominal aorta atherosclerosis, which may lead to an immune response. The present study obtained microarray data to investigate the gene expression differences underlying the potential pathogenesis of atherosclerosis and to elucidate the mechanisms underlying ATLO development. Microarray studies of the aorta, plaques, adventitia, blood, spleen, renal lymph nodes and ATLO were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in aorta clusters and ATLO clusters. Kyoto Encyclopedia of Genes and Genomes enrichment and Gene Ontology (GO) analyses were conducted to predict the biological functions of DEGs. The results demonstrated that interleukin 7 receptor (Il7r), C-X-C motif chemokine ligand (Cxcl)16, Cxcl13, Cxcl12, C-C motif chemokine receptor 2, C-C motif chemokine ligand (Ccl)8, Ccl5 and Ccl12 may function through pathways associated with ‘cytokine-cytokine receptor interaction’ and ‘chemokine signaling pathway’ in ATLO. Gene expression alterations were validated by reverse transcription-quantitative polymerase chain reaction. Il7r appeared to be the central gene involved in these events, and chemokines and/or chemokine receptors were visualized by GO enrichment. A protein-protein interaction network was constructed, which suggested that Il7r had a core function in all clusters. Taken together, the results indicated that Il7r upregulation may serve an important role in ATLO development via ‘cytokine-cytokine receptor interaction’ and ‘chemokine signaling pathway’. This may provide novel perspectives for understanding ATLO development and the regulation of the immune response in atherosclerosis.