Acod1, also known as immunoresponsive gene 1 (IRG1), is a mitochondrial enzyme responsible for catalyzing itaconate production. It plays a crucial role in immunometabolism, a field focusing on the relationship between metabolic pathways and immune responses. The upregulation of Acod1 expression in immune or non-immune cells is involved in metabolic reprogramming, signal transduction, inflammasome regulation, and protein modification [1,2,7].

In mouse models, Acod1-deficiency has diverse effects. In solid tumors, ACOD1-depleted human induced pluripotent stem cell-derived CAR-macrophages show enhanced pro-inflammatory state, with increased ROS production, phagocytosis, and cytotoxic functions against cancer cells, and better tumor repression in ovarian or pancreatic cancer mouse models [3]. In arthritis, Acod1-deficient mice exhibit increased osteoclast numbers and bone erosion, indicating Acod1's role in suppressing osteoclast differentiation by inhibiting succinate dehydrogenase-dependent ROS production and Hif1α-mediated aerobic glycolysis [4]. In atherosclerotic plaques, Ldlr-/-atherogenic mice transplanted with Acod1-/-bone marrow display a more stable plaque phenotype with smaller necrotic cores [5]. In microglia post spinal cord contusion, microglia with transcriptional blockage of ACOD1 show more severe neuroinflammation and oxidative stress [6]. In breast cancer, Acod1 ablation in neutrophils abates tumor-infiltrating neutrophil infiltration and constrains metastasis [8].

In conclusion, Acod1 is a key regulator in immunometabolism. Its functions are revealed through gene-knockout mouse models, which contribute to understanding its roles in various disease areas such as cancer, arthritis, atherosclerosis, and spinal cord injury. These findings provide insights into potential therapeutic strategies targeting Acod1 for treating these diseases.