Cytokine-like Roles for Metabolites in Immunity

• Published in: Molecular cell 2020-06, Vol.78 (5), p.814-823
• Main Authors: Zasłona, Zbigniew, O’Neill, Luke A.J.
• Format: Article
• Language: English
• Subjects: Animals; Carboxylic Acids - immunology; Carboxylic Acids - metabolism; Citric Acid Cycle; Cytokines - metabolism; Energy Metabolism; Humans; Immunity - immunology; Immunity - physiology; Inflammation - metabolism; Ketoglutaric Acids - immunology; Ketoglutaric Acids - metabolism; Lactic Acid - immunology; Lactic Acid - metabolism; Signal Transduction; Succinates - immunology; Succinates - metabolism; Succinic Acid - immunology; Succinic Acid - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2020.04.002

Metabolites have functions in the immune system independent of their conventional roles as sources or intermediates in biosynthesis and bioenergetics. We are still in the pioneering phase of gathering information about the functions of specific metabolites in immunoregulation. In this review, we cover succinate, itaconate, α-ketoglutarate, and lactate as examples. Each of these metabolites has a different story of how their immunoregulatory functions were discovered and how their roles in the complex process of inflammation were revealed. Parallels and interactions are emerging between metabolites and cytokines, well-known immunoregulators. We depict molecular mechanisms by which metabolites prime cellular and often physiological changes focusing on intra- and extra-cellular activities and signaling pathways. Possible therapeutic opportunities for immune and inflammatory diseases are emerging. Zaslona and O’Neill review succinate, itaconate, α-ketoglutarate, and lactate as examples of metabolites that can control cytokine production and may act like cytokines themselves. These newly emerged immune molecules can activate transcription factors, modify protein structure and function, and alter molecular and cellular signaling pathways.