The IDO/kynurenine pathway is now established as a major regulator of immune system function. The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids. The pathway is therefore positioned to mediate the effects of systemic inflammation or stress-induced steroids on tissue function and its expression increases with age. Disorders of the musculoskeletal system are a common feature of ageing and many of these conditions are characterized by an inflammatory state. In inflammatory arthritis and related disorders, kynurenine protects against the development of disease, while inhibition or deletion of IDO1 increases its severity. The long-term regulation of autoimmune disorders may be influenced by the epigenetic modulation of kynurenine pathway genes, with recent data suggesting that methylation of IDO may be involved. Osteoporosis is also associated with abnormalities of the kynurenine pathway, reflected in an inversion of the ratio between blood levels of the metabolites anthranilic acid and 3-hydroxy-anthranilic acid. This review discusses evidence to date on the role of the IDO/kynurenine pathway and the highly prevalent age-related disorders of osteoporosis and rheumatoid arthritis and identifies key areas that require further research.

中文翻译：

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IDO激活，炎症和肌肉骨骼疾病。

IDO /犬尿氨酸途径现已确立为免疫系统功能的主要调节剂。最初的酶吲哚胺2,3-二加氧酶（IDO1）由IFNγ诱导，而色氨酸2,3-二加氧酶（TDO）由皮质类固醇诱导。因此，该途径被定位为介导全身性炎症或应激诱导的类固醇对组织功能的影响，并且其表达随着年龄的增长而增加。肌肉骨骼系统疾病是衰老的常见特征，其中许多疾病都以炎症状态为特征。在炎性关节炎和相关疾病中，犬尿氨酸可预防疾病的发展，而抑制或删除IDO1则会增加其严重性。自身免疫性疾病的长期调节可能受到犬尿氨酸途径基因的表观遗传调控的影响，最近的数据表明可能涉及IDO的甲基化。骨质疏松症还与犬尿氨酸途径异常有关，这反映在代谢物邻氨基苯甲酸和3-羟基邻氨基苯甲酸的血液水平之间的比率倒置。这篇综述讨论了迄今为止有关IDO /犬尿氨酸途径以及骨质疏松症和类风湿关节炎高度流行的年龄相关疾病的作用的证据，并确定了需要进一步研究的关键领域。