IDO1: an important enzyme in tryptophan catabolism through the kynurenine pathway

Target Name: IDO1

NCBI ID: G3620

IDO1: an important enzyme in tryptophan catabolism through the kynurenine pathway

IDO1 can be upregulated by various factors such as IFN-gamma, TNF-alpha, and LPS, while downregulated by IL-4 and TGF-beta. Inhibitors of IDO1 have been extensively studied. IDO1 inhibitors can increase T-cell activation at the site of tumor cells, making them potential therapeutic agents for cancer treatment. Additionally, IDO1 activity plays a crucial role in the metabolism of tryptophan in the gastrointestinal tract, affecting mucosal defense, mucin production, and tight junction proteins. Furthermore, IDO1 is involved in the anti-T. gondii immune response and its growth inhibition in human cells. Combined neutralization of PD-L1 and TGF-beta1 with inhibition of IDO1 has been shown to reverse immune suppression in peritumoral cells.
In the context of the study, the researchers investigated the effects of kynurenic acid (KYNA), an IDO1 metabolite, on TSG-6 production in human umbilical cord mesenchymal stem cells (HUC-MSCs) through the activation of the aryl hydrocarbon receptor (AhR) signaling pathway. They found that MSCs expressed high levels of AhR compared to other receptors [6a]. KYNA treatment led to increased translocation of AhR to the nucleus, suggesting the activation of AhR signaling in MSCs [6b]. This was further supported by the increased expression of AhR-regulated metabolic enzymes, CYP1A1 and CYP1B1 [6c]. KYNA also enhanced the binding of AhR to the TSG-6 promoter, promoting TSG-6 expression [6e]. The researchers observed that KYNA treatment resulted in enhanced TSG-6 production by HUC-MSCs [6d]. Additionally, KYNA inhibited immune cell infiltration in a peritonitis model, further enhancing the therapeutic effect of HUC-MSCs [6, Supplementary Fig. 6]. Overall, KYNA, an IDO1 metabolite, was able to activate AhR signaling, leading to increased TSG-6 production in HUC-MSCs.

Protein Name: Indoleamine 2,3-dioxygenase 1

Functions: 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)

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