Itaconate: A key regulator of immune responses and potential therapeutic target for autoimmune and inflammatory diseases

Itaconate, a metabolite of the tricarboxylic acid cycle (TAC), has gained increasing attention in recent years due to its anti-inflammatory and immunomodulatory properties. It plays a crucial role in immune regulation by modulating signal transduction and posttranslational modification. Itaconate is derived from cis-aconitate decarboxylation and is produced by cis-aconitate decarboxylase (ACOD1) in the mitochondria. During cellular stress conditions, itaconate rapidly accumulates in myeloid cells. Recent studies have demonstrated that itaconate plays a pivotal role in modulating both innate and adaptive immune responses. Moreover, itaconate regulates the differentiation and function of innate immune and lymphoid cells, which is implicated in the pathogenesis of autoimmune diseases. In this review, we aim to explore the recent advancements in comprehending the functional regulation and mechanisms of itaconate in various populations of innate immune and lymphoid cells, as well as its immunomodulatory effects in the development of autoimmune diseases. In addition, we highlight the potential therapeutic applications of itaconate and its derivatives in autoimmune diseases.