Different partners, opposite outcomes: a new perspective of the immunobiology of indoleamine 2,3-dioxygenase

Mol Med. 2012 Jul 18;18(1):834-42. doi: 10.2119/molmed.2012.00029.

Abstract

Indoleamine 2,3-dioxygenase (IDO), a metabolic enzyme that catalyzes tryptophan conversion into kynurenines, is a crucial regulator of immunity. Altered IDO activity is often associated with pathology, including neoplasia and autoimmunity. IDO is highly expressed in dendritic cells (DCs) that exploit the enzyme's activity and the production of tryptophan catabolites to regulate immune responses by acting on several cell types, including T lymphocytes, of which they promote a regulatory phenotype. IDO also contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that, once bound by distinct molecular partners, will either promote degradation or initiate signaling activity and self-maintenance of the enzyme. We here discuss how ITIM-dependent molecular events can affect the functional plasticity of IDO by modifying the protein half-life and its enzymic and nonenzymic functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Dendritic Cells / enzymology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • I-kappa B Kinase / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Interleukin-6 / metabolism
  • NF-kappa B / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Proto-Oncogene Proteins c-fyn / metabolism
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-6
  • NF-kappa B
  • Receptors, Immunologic
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins c-fyn
  • Interleukin-1 Receptor-Associated Kinases
  • I-kappa B Kinase
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6