Acovic Aleksandar, Gazdic Marina, Jovicic Nemanja, Harrell C Randall, Fellabaum Crissy, Arsenijevic Nebojsa, Volarevic Vladislav
Center for Molecular Medicine and Stem Cell Research, Department of Microbiology and Immunology, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia.
Regenerative Processing Plant-RPP, LLC, Palm Harbor, Florida, USA.
Therap Adv Gastroenterol. 2018 Dec 6;11:1756284818815334. doi: 10.1177/1756284818815334. eCollection 2018.
Indoleamine 2,3-dioxygenase (IDO) has the most important role in modulation of tryptophan-dependent effects in the gastrointestinal tract, including modulation of intestinal immune response. An increased IDO activity maintains immune tolerance and attenuates ongoing inflammation but allows immune escape and uncontrolled growth of gastrointestinal tumors. Accordingly, IDO represents a novel therapeutic target for the treatment of inflammatory and malignant diseases of the gastrointestinal tract. In this review article, we summarize current knowledge about molecular and cellular mechanisms that are involved in IDO-dependent effects. We provide a brief outline of experimental and clinical studies that increased our understanding of how enhanced IDO activity: controls host-microbiota interactions in the gut; regulates detrimental immune response in inflammatory disorders of the gastrointestinal system; and allows immune escape and uncontrolled growth of gastrointestinal tumors. Additionally, we present future perspectives regarding modulation of IDO activity in the gut as possible new therapeutic approaches for the treatment of inflammatory and malignant diseases of the gastrointestinal system.
吲哚胺2,3-双加氧酶(IDO)在调节胃肠道中色氨酸依赖性效应方面发挥着最重要的作用,包括调节肠道免疫反应。IDO活性增加可维持免疫耐受并减轻正在进行的炎症,但会导致免疫逃逸和胃肠道肿瘤的失控生长。因此,IDO是治疗胃肠道炎症性和恶性疾病的一个新的治疗靶点。在这篇综述文章中,我们总结了目前关于IDO依赖性效应所涉及的分子和细胞机制的知识。我们简要概述了实验和临床研究,这些研究加深了我们对增强的IDO活性如何:控制肠道中的宿主-微生物群相互作用;调节胃肠道系统炎症性疾病中的有害免疫反应;以及导致胃肠道肿瘤的免疫逃逸和失控生长的理解。此外,我们还介绍了关于调节肠道中IDO活性作为治疗胃肠道系统炎症性和恶性疾病可能的新治疗方法的未来展望。