Abstract
Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that its effects include the emergence of a regulatory phenotype in naive CD4(+)CD25(-) cells via the general control non-depressing 2 (GCN2) protein kinase mediated induction of the forkhead transcription factor Foxp3. These cells are capable of effective control of diabetogenic T cells in vivo.
MeSH terms
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Animals
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Autoimmunity*
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Dendritic Cells / immunology
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Female
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism
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Immune Tolerance
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Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
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Mice
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Mice, Inbred DBA
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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Mice, Transgenic
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Models, Immunological
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism
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T-Lymphocytes, Regulatory / immunology*
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Tryptophan / immunology*
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Tryptophan / metabolism*
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Tryptophan
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Eif2ak4 protein, mouse
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Protein Serine-Threonine Kinases