Tregs have different metabolic profiles compared to CD4+ T effector cells. Tregs utilize FAO for their differentiation, unlike Teffs cells [54, 55]. Furthermore, Tregs depend on OXPHOS for proliferation and steady, long-lasting suppressive functions as seen in Tmems [23, 28]. In Tregs, FOXP3 expression use fatty acids, upregulate ETC, and ATP generation through OXPHOS. Moreover, FOXP3 initiates increased fatty acid β-oxidation, which results in the selective protection of FOXP3+ cells from fatty acid-induced cell death [56]. This phenomenon is crucial to provide a key target for modulating Treg function and selection in clinical settings. Recent findings have identified an inverse relation for the metabolic phenotype in mouse Tregs and human Tregs. In murine models, iTregs displayed low glycolytic rate, whereas, human iTregs, preferentially use glycolysis for their development and function because of enolase-1 suppresses the transcription of the exon 2-containing FOXP3 splicing variant unless engaged in glycolysis [32, 57]. This splicing variant is important for Treg mediated suppression.