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 language | English (US) |
|---|---|
| Pages (from-to) | 81-90 |
| Number of pages | 10 |
| Journal | Immunology Letters |
| Volume | 117 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 15 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Modulation of invariant natural killer T cell cytokine responses by indoleamine 2,3-dioxygenase
AU - Molano, Alberto
AU - Illarionov, Petr A.
AU - Besra, Gurdyal S.
AU - Putterman, Chaim
AU - Porcelli, Steven A.
PY - 2008/4/15
Y1 - 2008/4/15
N2 - 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.
AB - 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.
KW - Indoleamine 2,3-dioxygenase
KW - iNKT cells
KW - T cells
KW - Th1/Th2 cells
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=40649121252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40649121252&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2007.12.013
DO - 10.1016/j.imlet.2007.12.013
M3 - Article
C2 - 18272236
AN - SCOPUS:40649121252
VL - 117
SP - 81
EP - 90
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 1
ER -