Immune regulation through tryptophan metabolism

Amino acids are fundamental units of molecular components that are essential for sustaining life; however, their metabolism is closely interconnected to the control systems of cell function. Tryptophan (Trp) is an essential amino acid catabolized by complex metabolic pathways. Several of the resulting Trp metabolites are bioactive and play central roles in physiology and pathophysiology. Additionally, various physiological functions of Trp metabolites are mutually regulated by the gut microbiota and intestine to coordinately maintain intestinal homeostasis and symbiosis under steady state conditions and during the immune response to pathogens and xenotoxins. Cancer and inflammatory diseases are associated with dysbiosis- and host-related aberrant Trp metabolism and inactivation of the aryl hydrocarbon receptor (AHR), which is a receptor of several Trp metabolites. In this review, we focus on the mechanisms through which Trp metabolism converges to AHR activation for the modulation of immune function and restoration of tissue homeostasis and how these processes can be targeted using therapeutic approaches for cancer and inflammatory and autoimmune diseases. Tryptophan: Breakdown products influencing health and disease The dietary essential amino acid tryptophan is converted by cellular metabolism into breakdown products that play regulatory roles in health and disease, some involving their effects on a gene control protein called the aryl hydrocarbon receptor (AHR). Su-Kil Seo at Inje University, Busan, and Byungsuk Kwon at the University of Ulsan, in South Korea, review recent insights into the role of several catabolites (breakdown products) of tryptophan in regulating the AHR. The effects of aberrant tryptophan metabolism on the AHR can promote inflammatory diseases and cancers. In addition to the body’s own metabolism, tryptophan catabolites are produced by the body’s natural microbes. Many of the effects in health and disease involve regulation of the immune system. Drugs able to interact with the AHR protein could be potential treatments for a variety of inflammatory diseases.