EPA Induces an Anti-Inflammatory Transcriptome in T Cells, Implicating a Triglyceride-Independent Pathway in Cardiovascular Risk Reduction.

Twice-daily intake of purified eicosapentaenoic acid (EPA) reduces atherosclerotic cardiovascular disease risk in patients with high triglycerides, but its exact mechanism remains unclear. We exposed non-activated CD4 T cells to 100μM EPA, oleic acid, palmitic acid, or control, and conducted RNA and ATAC-sequencing after 48 hours. EPA exposure downregulated immune response-related genes like HLA-DRA, CD69, and IL2RA, and upregulated oxidative stress prevention genes like NQO1. Transcription factor footprinting showed decreased GATA3 and PU.1, and increased REV-ERB. These effects were specific to EPA, suggesting it induces an anti-inflammatory transcriptomic landscape in CD4 T cells, contributing to its observed cardiovascular benefits.