When immune cells are activated, they undergo metabolic change in order to have sufficient energy to function effectively. The Krebs cycle is one of the most important pathways involved in this response and citrate, a critical component of this pathway, regulates carbohydrate and lipid metabolism. Recently, citrate has also emerged as a key immunometabolite, exerting specific effects on immunity and inflammation. Citrate has been shown to be involved in the production of prostaglandins and nitric oxide, and via the generation of malonyl-CoA and acetyl-CoA in the cytosol, to impact cytokine production. Citrate can also generate itaconate via aconitate, which promotes an anti-inflammatory response. All these findings support citrate as a crucial signal for immune cell activation and function.
In this review we will describe the various ways through which citrate participates in immune cell behaviour and speculate on the targeting of citrate as a possible novel therapeutic approach for immune and inflammatory diseases.
Citrate; Krebs cycle; immunometabolism; itaconate; inflammation; ATP-citrate lyase