Modulation of invariant natural killer T cell cytokine responses by indoleamine 2,3-dioxygenase

Alberto Molano, Petr A. Illarionov, Gurdyal S. Besra, Chaim Putterman, Steven A. Porcelli

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The intracellular enzyme indoleamine 2,3-dioxygenase (IDO), which degrades the rare and essential amino acid tryptophan and converts it into a series of biologically active catabolites, has been linked to the regulation of immune tolerance by specific dendritic cell subsets, and to the downmodulation of exacerbated immune responses. Although the immunoregulatory effects of IDO may be in part due to generalized suppression of cell proliferation caused by tryptophan starvation, there is also evidence that tryptophan catabolites could be directly responsible for some of the observed effects. In this report, we investigated the consequences of IDO activity, particularly with regard to the effects of tryptophan-derived catabolites, on the cytokine responses of activated invariant natural killer T (iNKT) cells, a specialized T cell subset known to have immunoregulatory properties. Our results showed that pharmacologic inhibition of IDO skewed cytokine responses of iNKT cells towards a Th1 profile. In contrast, the presence at low micromolar concentrations of the tryptophan catabolites l-kynurenine, 3-hydroxy-kynurenine, or 3-hydroxy-anthranilic acid shifted the cytokine balance towards a Th2 pattern. These findings have implications for our current understanding of immunoregulation, and the mechanisms by which iNKT cells participate in the modulation of immune responses.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalImmunology Letters
Volume117
Issue number1
DOIs
StatePublished - Apr 15 2008

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Natural Killer T-Cells
Tryptophan
Cytokines
Kynurenine
Immune Tolerance
Essential Amino Acids
T-Lymphocyte Subsets
Starvation
Dendritic Cells
Cell Proliferation
Enzymes

Keywords

  • Indoleamine 2,3-dioxygenase
  • iNKT cells
  • T cells
  • Th1/Th2 cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Modulation of invariant natural killer T cell cytokine responses by indoleamine 2,3-dioxygenase. / Molano, Alberto; Illarionov, Petr A.; Besra, Gurdyal S.; Putterman, Chaim; Porcelli, Steven A.

In: Immunology Letters, Vol. 117, No. 1, 15.04.2008, p. 81-90.

Research output: Contribution to journalArticle

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