Van der Leek Aaron P, Yanishevsky Yarden, Kozyrskyj Anita L
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada.
Front Immunol. 2017 Nov 6;8:1374. doi: 10.3389/fimmu.2017.01374. eCollection 2017.
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.
在过去几十年里，色氨酸（TRP）代谢的犬尿氨酸（KYN）途径中的吲哚胺2,3-双加氧酶（IDO）亚群一直是免疫耐受领域众多研究的主题。在本综述中，我们旨在纳入关于该途径与过敏和肠道微生物群相关的新发现，同时对该途径本身进行全面概述。在干扰素γ的刺激下，IDO作为一种具有致耐受性的免疫抑制酶，通过诱导KYN-IDO途径、导致TRP耗竭以及KYN代谢产物升高来减轻过敏反应。KYN代谢产物通过芳烃受体发挥作用，引起T细胞无反应性和凋亡、调节性T细胞（Treg）和辅助性T细胞17（Th17）的增殖以及Th1/Th2反应的偏移，尽管结果高度依赖于微环境。此外，来自无菌小鼠和人类婴儿的新证据表明，肠道微生物群和母乳是决定KYN-IDO途径功能的关键因素。因此，我们建议进一步研究该途径如何可能成为微生物群与过敏发展之间的关键联系。
