Integrated transcriptomic, metabolomic and lipidomic analysis revealed unique metabolic profile of regulatory T cells upon activation 3421

Abstract Description Regulatory T cells (Tregs) are identified as CD4+CD25+CD127low population and characterized by stable FOXP3 expression. Tregs play a central role in the maintenance of immune tolerance and immune homeostasis in vivo through their suppressive activity. Unique metabolic properties of Tregs are previously shown such as reduced glycolysis and increased oxidative phosphorylation, however, the biological role of lipid metabolism in Tregs is still unknown. To dissect metabolic dynamics of Tregs, we have analyzed the gene expression and metabolic status of Tregs before and after TCR stimulation by combining transcriptomics, metabolomics and lipidomics. Integrated analysis showed that freshly isolated Tregs have both unique metabolomic and lipidomic properties. Moreover, integrated metabolomic and lipidomic analysis provided more distinct metabolic property of activated Tregs compared to activated Teffs. Interestingly, activated Tregs contained omega-3 polyunsaturated fatty acids enriched triglycerides including EPA and DHA. Transcriptomics also supported these results by increased CD36 and PPAR-gamma expressions. By confocal microscopy, Tregs showed enriched lysosomes and peroxisomes compared to Teffs upon activation. Our data confirmed that Tregs exhibit unique lipidomic profiles characterized by enriched omega-3 polyunsaturated fatty acids triglycerides, together with enriched lysosomes and peroxisomes which correspond to metabolic alterations. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)