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Vaccines (Basel). 2015 Sep 10;3(3):703-29. doi: 10.3390/vaccines3030703.

The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity.

Author information

1
Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. jmbongue@llu.edu.
2
Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. dnicholas@llu.edu.
3
California Baptist University, Riverside, CA 92504, USA. t2torrez722@gmail.com.
4
Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. nkim@llu.edu.
5
Department of Molecular Biology, Chonbuk National University, Jeon-Ju 54896, Korea. nkim@llu.edu.
6
Endocrinology Section, JL Pettis Memorial VA Medical Center, Loma Linda, CA 92357, USA. Anthony.firek@va.gov.
7
Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. blangridge@llu.edu.

Abstract

Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called "kynurenines" that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells.

KEYWORDS:

CTB-INS; Indoleamine 2, 3-dioxygenase; NF-κB; Tryptophan; Vaccine

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