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

“Mesenchymal stem cells provide a basis for improved tissue regeneration and gene therapy [17,18].”

“Several molecular stimuli and signaling pathways were shown to induce the transcription and translation of metabolically-active IDO1 enzyme [35,40,50].”

“About 80% of patients are women with a 2–5-times greater risk of autoimmune disease onset among African, Hispanic and Native American women than those of European descent [119,137,143–145].”

“confirming that placental cells synthesizing IDO1 can protect the mammalian fetus from maternal T-cell attack [15,16].”

“A connection between elevated urinary tryptophan catabolites and bladder cancer was first reported in the 1950s [105].”

“Mesenchymal stem cells provide a basis for improved tissue regeneration and gene therapy [17,18].”

“The aryl hydrocarbon receptor (AhR) was shown to cause immune suppression after binding dioxin [70].”

“Interestingly, kynurenines produced from IDO’s enzymatic activity can also bind and activate as an endogenous ligand, AhR [53,54].”

“self-antigens were shown to prevent uveitis, multiple sclerosis and type 1 diabetes in animal models of autoimmunity [124,131,132,142,153].”

“Type 1 diabetes (T1D) is a well-studied prototypic tissue-specific autoimmune disease resulting from auto-reactive lymphocyte destruction of the pancreatic islet insulin-producing -cells [34,134–137].”

“Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan degradation into kynurenine and related metabolites, contributing to immune suppression by limiting T-cell activity and generating immunoregulatory byproducts [4].”

“Cytokines such as TGF-β , IL-10, and IDO (indoleamine 2,3-dioxygenase) further suppress this, creating an environment that shuts down normal immune functions [113,114].”

“The IDO1 enzyme that catalyzes tryptophan (l-Trp) degradation together with the kynurenine pathway [6] is induced by pro-inflammatory cytokines during chronic inflammation, e.g., in the case of aging and age-associated diseases [7–10].”

“The splenic toxicity of the lymphocyte due to perturbation in the antioxidant/oxidative stress redox was evident in recent studies (Jacques et al., 2015; Qu et al., 2019; Zhao & Zhang, 2018).”

“[39].”

“It is thought to play a role in a variety of pathophysiological processes, including antimicrobial and antitumor defense, neuropathology, immune-regulation, antioxidant activity, and autoimmunity suppression (22).”

“MDSCs suppress T cell activation and proliferation through upregulation of reactive oxygen species (ROS) and arginase, as well as indoleamine 2,3-dioxygenase (IDO) [22-24] which suppresses T-cell function by converting essential tryptophan into suppressive kynurenines [25].”

“The HPV can evade the cytotoxic action of NK cells al o by changes of IDO (indoleamine 2,3- Dioxygenase) immunosuppressive enzyme (Amador-Molina et al., 2013; Mbongue et al., 2015).”

“However, IDO1 is not vital for regulation of self-tolerance as IDO1 knock out mice (IDO) do not die from autoimmune responses [167].”