The Function of IDO1
Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885).
Protein names
Recommended name:
Indoleamine 2,3-dioxygenase 1Short name:
IDO-1Alternative name(s):
Indoleamine-pyrrole 2,3-dioxygenaseTop Gene-Substance Interactions
IDO1 Interacts with These Diseases
| Disease | Score |
Substances That Increase IDO1
| Substances | Interaction | Organism | Category |
Substances That Decrease IDO1
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Expressed in mature dendritic cells located in lymphoid organs (including lymph nodes, spleen, tonsils, Peyers's patches, the gut lamina propria, and the thymic medulla), in some epithelial cells of the female genital tract, as well as in endothelial cells of term placenta and in lung parenchyma (PubMed:25691885). Weakly or not expressed in most normal tissues, but mostly inducible in most tissues (PubMed:25691885). Expressed in more than 50% of tumors, either by tumoral, stromal, or endothelial cells (expression in tumor is associated with a worse clinical outcome) (PubMed:18418598). Not overexpressed in tumor-draining lymph nodes (PubMed:26155395, PubMed:25691885).
Gene Pathways:
Induction:
By IFNG/IFN-gamma in most cells (PubMed:2109605, PubMed:1907934). Exogenous inflammatory stimuli induce the expression of IDO1 in antigen-presenting cells such as dendritic cells, macrophages and B-cells (PubMed:25157255).
Enzyme Regulation:
Activity is inhibited by and MTH-trp (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan).
Cofactor:
Binds 1 heme group per subunit (PubMed:16477023, PubMed:25313323). In the active form, the heme iron is in its ferrous state Fe(+2). The catalytic cycle does not alter the oxidation state of the heme, but IDO1 is prone to autoxidation (PubMed:16574111).
Molecular Function:
- Electron Carrier Activity
- Heme Binding
- Indoleamine 2,3-Dioxygenase Activity
- Metal Ion Binding
- Tryptophan 2,3-Dioxygenase Activity
Biological Processes:
- Cytokine Production Involved In Inflammatory Response
- Female Pregnancy
- Immune System Process
- Kynurenic Acid Biosynthetic Process
- Multicellular Organismal Response To Stress
- Negative Regulation Of Interleukin-10 Production
- Negative Regulation Of T Cell Apoptotic Process
- Negative Regulation Of T Cell Proliferation
- Positive Regulation Of Chronic Inflammatory Response
- Positive Regulation Of Interleukin-12 Production
- Positive Regulation Of T Cell Apoptotic Process
- Positive Regulation Of T Cell Tolerance Induction
- Positive Regulation Of Type 2 Immune Response
- Response To Lipopolysaccharide
- Swimming Behavior
- Tryptophan Catabolic Process
- Tryptophan Catabolic Process To Kynurenine