Abstract
The aryl hydrocarbon receptor (AHR) has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3(+) regulatory T cells (Tregs) versus Th17 cells. In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent Treg generation. We additionally investigate the dependence of TGF-beta on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells postexposure to TGF-beta. These results shed light on the relationship of IDO to the generation of Tregs, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Line, Tumor
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Cells, Cultured
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Coculture Techniques
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Dendritic Cells / enzymology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dose-Response Relationship, Immunologic
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Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
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Indoleamine-Pyrrole 2,3,-Dioxygenase / physiology
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Kynurenine / chemistry
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Kynurenine / metabolism*
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Kynurenine / physiology
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Ligands
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Aryl Hydrocarbon / deficiency
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Receptors, Aryl Hydrocarbon / metabolism*
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Receptors, Aryl Hydrocarbon / physiology
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Signal Transduction / immunology
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T-Lymphocytes, Regulatory / cytology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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Transforming Growth Factor beta / physiology
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Tryptophan / chemistry
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Tryptophan / physiology
Substances
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Ligands
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Receptors, Aryl Hydrocarbon
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Transforming Growth Factor beta
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Kynurenine
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Tryptophan