Extended Data Fig. 8: Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics.

By balancing glucose flux between glycolysis and PPP as well as carbons feeding into the TCA cycle in Tregs, TKT in non-oxidative PPP controls Treg function by maintaining metabolite-dependent functional gene expression. In the absence of TKT, reduced glucose catabolism triggers excessive amino acids and fatty acids to compensatorily feed into mitochondria, which further impairs mitochondrial function and energy production. Meanwhile, enhanced oxidative stress triggers reductive TCA cycle and reduces α-ketoglutarate/succinate and α-ketoglutarate/fumarate ratios, leading to increased DNA methylation, further limiting aTreg-associated functional gene expression and suppressive activity in Tregs.