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The kynurenine system and immunoregulation

  • Basic Neurosciences, Genetics and Immunology - Review article
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Abstract

There is developing interest in the role of the kynurenines in the immune function. A considerable amount of evidence has accumulated as concerns interactions between the kynurenine pathway, cytokines and the nervous system. Indoleamine 2,3-dioxygenase (IDO) occupies a key position connecting the immune system and the kynurenine pathway. There are evidences of the immunosuppressive effect of IDO. Following the interferon (IFN)-mediated activation of antigen presenting cells, the induction of IDO and the kynurenine system exerts a counter-regulating effect, maintaining the homeostasis. Inhibition of T cell functions, activation of the regulatory T cells, and the inhibition of Natural Killer cells are among the important factors in the immunosuppressive effects of IDO and kynurenines. There is a close connection between cytokines (IFN-α, IFN-γ, TNF-α, TGF-β, IL-4 and IL-23) and the kynurenine system, and an imbalance in the TH1/TH2 cytokine profile may possibly lead to neurologic or psychiatric disorders. As the tryptophan metabolic pathway is activated by pro-inflammatory stimuli, the anti-inflammatory effect of kynurenic acid provides a further feedback mechanism in modulating the immune responses.

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Abbreviations

IDO:

Indoleamine 2,3-dioxygenase

TRY:

Tryptophan

KYN:

Kynurenine

KYNA:

Kynurenic acid

KMO:

Kynurenine 3-monooxygenase

KH:

KYN3-hydrolase

3-OH KYN:

3-Hydroxykynurenine

KYNU:

Kynureninase

3-HAA:

3-Hydroxyanthranilic acid

HAAO:

3-Hydroxyantranilate 3,4-dioxygenase

QUIN:

Quinolinic acid

NMDA:

N-methyl-d-aspartate

α7-nACh:

α7-Nicotinic acethylcholine

NK cells:

Natural killer cells

DC:

Dendritic cell

Treg :

Regulatory T cells

PMNs:

Polymorphonuclear cells

IFN:

Interferon

TNF-α:

Tumor necrosis factor-α

TGF-β:

Transforming growth factor-β

IL:

Interleukin

IL-2:

Interleukin-2

CSF:

Cerebrospinal fluid

CNS:

Central nervous system

5-HT:

Serotonin

BBB:

Blood brain barrier

HMGB1:

High-mobility group box protein 1

HNP1-3:

Human neutrophil peptide 1-3

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, 6720, Szeged, Hungary

    Yvette Mándi

  2. Department of Neurology, University of Szeged, Szeged, Hungary

    László Vécsei

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  1. Yvette Mándi
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  2. László Vécsei
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Correspondence to Yvette Mándi.

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Mándi, Y., Vécsei, L. The kynurenine system and immunoregulation. J Neural Transm 119, 197–209 (2012). https://doi.org/10.1007/s00702-011-0681-y

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