Fig. 4
From: Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential
Overview of Treg metabolism. Foxp3 expression in Tregs is modulated by nutrient metabolites, intracellular metabolic intermediates, and signaling pathways. The vitamin A derivative RA promotes iTreg differentiation by enhancing TGF-β signaling via ERK1/2. Vitamin C stabilizes Foxp3 by demethylating CNS2. 1,25(OH)₂D₃ promotes Foxp3 expression by binding to the VDRE region. FABP5 inhibition enhances Treg suppressive function by activating the cGAS-STING signaling pathway. Upon TCR stimulation, ZFP91 translocates to the cytoplasm, facilitating BECN1-PIK3C3 complex formation and enhancing TCR-induced autophagy, supporting Treg metabolism and function. LKB1 maintains Foxp3 stability by inhibiting STAT4-driven CNS2 methylation and activating the mevalonate pathway, which results in the production of metabolites such as cholesterol and GGPP. Blimp1 inhibits Dnmt3a upregulation and prevents CNS2 methylation at the Foxp3 locus, thereby maintaining Treg stability and function. SCD1 deficiency upregulates ATP2A2, which, upon TCR activation, enhances the calcium–NFAT1–Foxp3 axis, promoting Treg differentiation. This figure was created with Biorender.com
