Indoleamine 2, 3-Dioxygenase: A Professional Immunomodulator and Its Potential Functions in Immune Related Diseases

Indoleamine 2, 3-dioxygenase (IDO) as an intracellular cytosolic enzyme converts tryptophan (Trp) to N-formyl kynurenine which leads to proinflammatory T-cell apoptosis and prevention of immune cells maturation via decreasing the level of cellular energy. Trp catabolism products such as kynurenine i...

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Bibliographic Details
Published in:International reviews of immunology 2022-05, Vol.41 (3), p.346-363
Main Authors: Heidari, Fahimeh, Ramezani, Amin, Erfani, Nasrollah, Razmkhah, Mahboobeh
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
autoimmunity
Humans
Immune System Diseases
Immunologic Factors - pharmacology
Immunologic Factors - therapeutic use
immunomodulatory
immunotherapy
Indoleamine 2, 3-dioxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Kynurenine - metabolism
Neoplasms
Tryptophan - metabolism
Tumor Microenvironment
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Summary:Indoleamine 2, 3-dioxygenase (IDO) as an intracellular cytosolic enzyme converts tryptophan (Trp) to N-formyl kynurenine which leads to proinflammatory T-cell apoptosis and prevention of immune cells maturation via decreasing the level of cellular energy. Trp catabolism products such as kynurenine increase the recruitment of regulatory T cells and induce immune tolerance in dendritic cells. IDO expression can locally suppress immunity in the tumor microenvironment and tumor progression actively recruits IDO expressing cells in tumor-draining lymph nodes. Also, tumor infiltrating Tregs' activity leads to IDO expression in the tumor microenvironment. In this review, we described the immunomodulatory function of IDO and IDO-based therapeutic strategies for immune related diseases. According to positive-feedback loop between Tregs and IDO in the tumor microenvironment, IDO can be targeted as a promising immunostimulatory approach for immunotherapy of cancer. However, several studies revealed controversial consequences for influences of IDO in immunity. Considering the common concept, IDO1 and also IDO2 repress the function of T lymphocytes, while inactivation of IDO results in aggravation of some autoimmune diseases. Eventually, the extensive evaluation of IDO function in immunomodulatory procedure can help achieve IDO inhibitors as optimal drugs to inhibit tumor growth without motivating autoimmunity.
ISSN:0883-0185
1563-5244
DOI:10.1080/08830185.2020.1836176