Combined transcriptomic and lipidomic analysis reveals enhanced lipogenesis in memory Tregs upon TCR activation

Regulatory T cells (Tregs) maintain immune homeostasis in vivo. Similar to conventional T cells (Tconvs), Tregs are divided into naïve and memory cells. Tregs have unique metabolic properties, including enhanced oxidative phosphorylation. The lipidomic profiles of human Tregs have been studied previously; however, those of naïve and memory Tregs have not yet been consistently compared. Thus, in the present study, we used a combined transcriptomic and lipidomic analysis to assess the metabolic features of human naïve and memory Tregs upon activation. Using transcriptomic analysis, we identified distinct gene expression profiles in naïve and memory Tregs compared with those in Tconvs. Upon TCR stimulation, memory Tregs showed a lipidomic profile distinct from that of memory Tconvs, whereas the lipidomic profiles of naïve Tregs were similar to those of naïve Tconvs. Furthermore, upon TCR stimulation, memory Tregs expressed triglycerides (TGs) that were more enriched in monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) than those of memory Tconvs. However, memory Tconvs also had higher PUFA-TG levels than naïve Tconvs and Tregs after TCR stimulation, although their levels remained lower than those in memory Tregs. These findings suggest PUFA-TGs could be a marker of memory Tregs. In turn, higher frequency of memory cells within the Treg population may also contribute to the observed enrichment of PUFA-TGs in Tregs upon TCR activation. Our study demonstrated unique transcriptomic and lipidomic profiles and enhanced lipogenesis in memory Tregs upon TCR stimulation.