Endothelial Cells Exhibit Persistent Inflammation-Mediated Immunological Memory, affecting Infectious and Vascular Disease-Associated Pathways [RNA-Seq]

ABSTRACT: Chronic inflammation characteristic for infectious and inflammatory disease is mediated by hyperproduction of proinflammatory cytokines and increased cytokine-mediated crosstalk between innate immune cells and the endothelial lining. Although there is increasing evidence that adaptive and innate immune cells can develop ‘immunological memory’ by ‘immune training’, little is known whether in endothelial cells this process also takes place. We investigated whether endothelial cells develop ‘cytokine memory’ by repeatedly exposing them to IFN-γ and TNF-α, key cytokines involved in the regulation of chronic inflammation. Global transcriptome and chromatin accessibility assessment (ATAC-seq) upon repeated stimulation revealed all characteristics for immune training phenotypes (priming, training, and tolerance). In addition to enhanced induction of HLA genes, cytokine-dependent expression, and opening of chromatin regions associated with immune response genes were observed in endothelial cells upon training. Twenty genes, including TLR2, IL1B, and HDAC9, that are known to be involved in inducing training of innate immune cells, also showed the “trained immunity” pattern upon TNF-α stimulation in endothelial cells. Using an advanced 3D vessel-on-chip model, we further show that a significantly higher number of monocytes adhere to trained endothelial cells. Importantly, we found several differentially opened chromatin regions harboring SNPs associated with COVID-19, sepsis, and cardiovascular diseases. In summary, our findings show that endothelial cells also exhibit a “trained immunity” response upon chronic inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267418 | GEO | 2025/05/14

REPOSITORIES: GEO