The kynurenine system and immunoregulation

J Neural Transm (Vienna). 2012 Feb;119(2):197-209. doi: 10.1007/s00702-011-0681-y. Epub 2011 Jul 9.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Tolerance / immunology*
  • Immunomodulation / physiology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / physiology
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Kynurenine / metabolism
  • Kynurenine / physiology*
  • Kynurenine / therapeutic use*
  • Neural Pathways / enzymology
  • Neural Pathways / immunology
  • Neural Pathways / pathology
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Kynurenine