Indoleamine 2, 3-dioxygenase regulation of immune response (Review)

Abstract

Indoleamine 2, 3-dioxygenase (IDO) catalyzes the initial and rate‑limiting step in the degradation pathway of the essential amino acid tryptophan and is expressed by professional antigen presenting cells (APCs), epithelial cells, vascular endothelium and tumor cells. IDO‑mediated catabolic products, which are additionally termed 'kynurenines', exerts important immunosuppressive functions primarily via regulating T effector cell anergy and inducing the proliferation of T regulatory cells. This endogenous tolerogenic pathway has a critical effect on mediating the magnitude of immune responses under various stress conditions, including tumor, infection and transplantation. The present review evaluates the recent progress in elucidating how catabolism of tryptophan regulated by IDO modulates the immune response to inflammatory and immunological signals. Blocking this pathway may be a novel adjuvant therapeutic strategy for clinical application in immunotherapy.

Assessment of neopterin and indoleamine 2,3‐dioxygenase activity in patients with seasonal influenza: A pilot study

“…Increased levels of neopterin have previously also been associated with adverse outcomes in different diseases including viral infections . Similarly, tryptophan metabolism is able to slow down cellular immune response, for example, during infections, and thus, the determination of tryptophan metabolites may hold promise to predict outcomes in viral infections …”

“…8,[16][17][18] Similarly, tryptophan metabolism is able to slow down cellular immune response, for example, during infections, and thus, the determination of tryptophan metabolites may hold promise to predict outcomes in viral infections. 19 Since influenza antigen bed-side tests have limited sensitivity and polymerase chain reaction (PCR)-based methods are expensive and often not available, cheaper and more reliable biomarkers for diagnosis, and risk stratification of patients with influenza infection are desired. 20 The aim of this pilot study was to investigate neopterin levels and IDO activity in sera of hospitalized patients with influenza infection and to analyze correlations with clinical outcome parameters in a small real-life cohort.…”

Immunoregulatory effect of mouse fetal neural cells on the graft-versus-host disease

“…The use of the specific cryopreservation regime contributed to the redistribution of FNCs subpopulation into the glial cells, which, under the impact of one of the most powerful inflammatory mediators, IFN-γ, could increase the gene expression and the production of IDO [16]. The effect of this enzyme may enhance expression of FOXP3 transcription factor in naive CD4 + cells and differentiation of Treg [21]. Since in FNCs of the 12th day of gestation, which are transplanted for the treatment of GVHD, in addition to the micro-and macroglia as a potential IDO producers, there are also dendritic cells [39], whose participation in the differentiation of FOXP3 + Treg in the recipient is not excluded.…”

“…Another aspect of the immunoregulatory effects of IDO is to stimulate the differentiation of naive CD4 + cells in Treg cells. In particular, kynurenine and its derivatives in combination with TGF-ß promote the activation of foxp3 gene acting through AhR, which causes the formation of the Treg subpopulation [21]. Kynurenine pathway of tryptophan degradation is the most common in macrophages and microglial cells [22] and partly in astrocytes [23].…”

Endothelial cell and T‐cell crosstalk: Targeting metabolism as a therapeutic approach in chronic inflammation

“…The enzyme is responsible for extra-hepatic catabolic degradation of tryptophan, and it is expressed in vascular endothelium, professional antigen-presenting cells, epithelial cells, and tumour cells (Gerriets & Rathmell, 2012). IDO is produced after ECs are triggered by IFN-γ and/or TNF-α (Mbongue et al, 2015) and is considered a major inhibitor of the immune response, as it appears to restrict potentially exaggerated inflammatory reactions (Wu, Gong, & Liu, 2018 (Boussouar & Benahmed, 2004), a modulator of energy production (Chari, Lam, Wang, & Lam, 2008), and a signalling molecule (Philp, Macdonald, & Watt, 2005). Interestingly, lactate modulates Tcell function directly via specific cell surface lactate transporters.…”