Modulation of T cells by tryptophan metabolites in the kynurenine pathway

Abstract

Lymphocytes maturing in the thymus (T cells) are key factors in adaptive immunity and the regulation of inflammation. The kynurenine pathway of tryptophan metabolism includes several enzymes and compounds that can modulate T cell function, but manipulating these pharmacologically has not achieved the expected therapeutic activity for the treatment of autoimmune disorders and cancer. With increasing knowledge of other pathways interacting with kynurenines, the expansion of screening methods, and the application of virtual techniques to understanding enzyme structures and mechanisms, details of interactions between kynurenines and other pathways are being revealed. This review surveys some of these alternative approaches to influence T cell function indirectly via the kynurenine pathway and summarizes the most recent work on the development of compounds acting directly on the kynurenine pathway.

Keywords: 3-hydroxyanthranilic acid; AHR; GPR35; IDO; IL4i1; T cells; autoimmunity; cancer therapy; immune tolerance; indoleamine 2,3-dioxygenase; kynurenic acid; kynurenine; tryptophan.