[Research progress of itaconate on the regulation of macrophage inflammation]

Macrophages are important innate immune cells. Under inflammatory stimulation, macrophages rapidly respond and subsequently produce large amounts of cellular metabolites through metabolic reprogramming. Itaconate is an immunomodulatory derivative from the tricarboxylic acid cycle which has antioxidative and anti-inflammatory effects. In recent years, it has been reported that itaconate promotes the transition of macrophage phenotype from M1 to M2 and the underlying mechanism may include the activation of nuclear factor E2-related factor 2 (Nrf2) by alkylation of Kelch-like ECH-associated protein 1 (Keap1), inhibition of succinate dehydrogenase (SDH) and reactive oxygen species (ROS), blockade of the inhibitor ζ of nuclear factor-κB (IκBζ) translation and inhibition of aerobic glycolysis. In this review, we describe the metabolic pathways of itaconate, clarify the relationship between itaconate and the immune response, and summarize the latest researches about the roles of itaconate on regulating the inflammatory response in macrophages in order to provide the basis for the clinical use of itaconate and new strategies for the treatment of inflammatory diseases.