Department of Microbiology and Immunology, College of Medicine Inje University, Busan, 47392, Republic of Korea.
Parenchyma Biotech, Busan, 47392, Republic of Korea.
Exp Mol Med. 2023 Jul;55(7):1371-1379. doi: 10.1038/s12276-023-01028-7. Epub 2023 Jul 3.
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.
氨基酸是分子成分的基本单位，对维持生命至关重要；然而，它们的代谢与细胞功能的控制系统密切相关。色氨酸（Trp）是一种必需氨基酸，通过复杂的代谢途径进行分解代谢。产生的几种 Trp 代谢物是生物活性的，在生理学和病理生理学中发挥核心作用。此外，Trp 代谢物的各种生理功能受肠道菌群和肠道的相互调节，以在稳态条件下以及在对病原体和外毒素的免疫反应期间协调地维持肠道内稳态和共生。癌症和炎症性疾病与肠道菌群失调和宿主相关的异常 Trp 代谢以及芳香烃受体（AHR）失活有关，AHR 是几种 Trp 代谢物的受体。在这篇综述中，我们重点讨论了 Trp 代谢如何汇聚到 AHR 激活以调节免疫功能和恢复组织内稳态的机制，以及如何使用癌症和炎症性及自身免疫性疾病的治疗方法来靶向这些过程。
