Abstract
In the past few decades, the indoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites. Acting through the aryl hydrocarbon receptor, KYN metabolites cause T-cell anergy and apoptosis, proliferation of Treg and Th17 cells, and deviation of the Th1/Th2 response, although the outcome is highly dependent on the microenvironment. Moreover, new evidence from germ-free mice and human infants shows that gut microbiota and breast milk are key in determining the functioning of the KYN-IDO pathway. As such, we recommend further research on how this pathway may be a critical link between the microbiome and development of allergy.
Highlights
The indolamine 2,3-dioxegenase (IDO) subset of the kynurenine (KYN) pathway of tryptophan (TRP) degradation has long been acknowledged to contribute substantially to the control of general inflammation [1]
KYN catabolites were viewed as inert precursors for the formation of nicotinic acid dinucleotide (NAD)+, but newer findings have identified a number of physiological effects for these metabolites
Accumulating evidence is solidifying the role of the KYN-IDO pathway as an immunosuppressive pathway, which exhibits tolerogenic effects in response to stimuli through T-cell suppression, anergy, differentiation, and apoptosis
Summary
The indolamine 2,3-dioxegenase (IDO) subset of the kynurenine (KYN) pathway of tryptophan (TRP) degradation has long been acknowledged to contribute substantially to the control of general inflammation [1]. Microbial exposure and resultant stimulation of the KYN-IDO pathway by Toll-like receptors (TLR) may work in conjunction with the hygiene hypothesis to determine the outcome of allergy, autoimmunity, and other disease [3]. Current evidence is promising to suggest that induction of the KYN-IDO pathway and resultant depletion of serum TRP and increase of TRP metabolites controls the allergic state [4]. This evidence, along with knowledge on the mechanism for IDO. Essential to understanding the immunomodulatory effects of TRP, Box 1 describes basic elements of its fate in the body and the KYN pathway
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