Tryptophan and indole metabolism in immune regulation. (June 2021)

• Record Type: Journal Article
• Authors: Fiore, Alessandra; Murray, Peter J
• Is Part Of: Current opinion in immunology. Volume 70(2021)
• Page Start: 7
• Page End: 14
• Publication Date: 2021-06
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2020.12.001
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: Tryptophan follows three metabolic fates: incorporation into proteins, production of indoles, and breakdown into kynurenine. IDO1 is an endogenous mechanism of peripheral tolerance and immunosuppression. Need to develop new ways of manipulating the IDO1 pathway and biochemical monitoring of tryptophan metabolism. Abstract : L-tryptophan is an essential amino acid that undergoes complex metabolic routes, resulting in production of many types of signaling molecules that fall into two types: retaining the indole ring such as serotonin, melatonin and indole-pyruvate or breaking the indole ring to form kynurenine. Kynurenines are the precursor of signaling molecules and are the first step in de novo NAD + synthesis. In mammalian cells, the kynurenine pathway is initiated by the rate-limiting enzymes tryptophan-2, 3-dioxygenase (TDO) and interferon responsive indoleamine 2, 3-dioxygenase (IDO1) and is the major route for tryptophan catabolism. IDO1 regulates immune cell function through the kynurenine pathway but also by depleting tryptophan in microenvironments, and especially in tumors, which led to the development of IDO1 inhibitors for cancer therapy. However, the connections between tryptophan depletion versus product supply remain an ongoing challenge in cellular biochemistry and metabolism. Here, we highlight current knowledge about the physiological and pathological roles of tryptophan signaling network with a focus on the immune system.