IL-7δ5 protein is expressed in human tissues and induces expression of the oxidized low density lipoprotein receptor 1 (OLR1) in CD14+ monocytes

Abstract Objectives The 6 exon spanning ́canonical‘ Interleukin-7 (IL-7c) is a non-redundant cytokine in human T-cell homeostasis that undergoes extensive alternative pre-mRNA splicing. The IL-7 gene variant lacking, exon 5 (IL-7δ5), exhibits agonistic effects as compared to IL-7c. We studied in this report for the first time the protein expression of IL-7δ5 variant in tissues and its role in monocyte activation. Methods We visualized the expression of IL-7δ5 protein by immunohistochemistry in both healthy and malignant (human) tissues and investigated the impact of IL-7δ5 stimulation on CD14+ monocytes using gene expression analysis and flow cytometry. Results IL-7≏5 is largely expressed by human epithelial cells, yet also by stromal cells in malignant lesions. Gene expression analysis in CD14+ monocytes, induced by the 6-exon spanning IL-7 or IL-7δ5 showed similar changes resulting in a pro-inflammatory phenotype and increased expression of genes involved in lipid metabolism. IL7≏5 was superior in inducing upregulation of the oxidised low density lipoprotein receptor (OLR), measured by flow cytometry, in CD14+ cells. Conclusion IL-7≏5, produced from non-transformed and transformed cells, may contribute to chronic inflammatory responses and development of ‘foamy’ cells by increased OLR1 expression that mediates increased oxLDL uptake.