itaconate

Itaconate is an endogenous metabolite and immunometabolic regulator that plays a critical role in guiding CD8+ T cell memory differentiation. Produced during immune responses, itaconate acts as an epigenetic modulator by directly binding to and inhibiting the lysine demethylase 5B (KDM5B). It functions as a competitive antagonist of alpha-ketoglutarate (α-KG), thereby preventing KDM5B-dependent demethylation of H3K4me3 and increasing chromatin accessibility at genes essential for memory T cell (TM) differentiation. Beyond its epigenetic effects, itaconate drives metabolic reprogramming by redirecting glucose flux from glycolysis to the pentose phosphate pathway (PPP), which sustains high levels of NADPH and glutathione to alleviate oxidative stress. This dual mechanism enhances the stem-like phenotype and persistence of T cells, making itaconate a potential therapeutic agent for improving the efficacy of CAR T cell therapies in treating viral infections and cancer.

Other names

itaconic acid2-methylidenebutanedioic acid