EPA induces an anti-inflammatory transcriptome in T cells, implicating a triglyceride-independent pathway in cardiovascular risk reduction

Abstract

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 100mM 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 antiinflammatory transcriptomic landscape in CD4+ T cells, contributing to its observed cardiovascular benefits. (JACC Basic Transl Sci. 2025;10:383-395) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).