The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation

Wei Chen, Xueqing Liang, Amanda J. Peterson, David H Munn, Bruce R. Blazar

Research output: Contribution to journalArticle

287 Citations (Scopus)

Abstract

Human plasmacytoid dendritic cells (PDCs) can drive naive, allogeneic CD4+CD25+ T cells to differentiate into CD4 +CD25+. Foxp3+ regulatory T cells (Tregs). However, the intracellular mechanism or mechanisms underlying PDC-induced Treg generation are unknown. In this study, we show that human PDCs express high levels of IDO, an intracellular enzyme that catabolizes tryptophan degradation. Triggering of TLR 9 with CpG oligodeoxynucleotides activates PDCs to up-regulate surface expression of B7 ligands and HLA-DR Ag, but also significantly increases the expression of IDO and results in the generation of inducible Tregs from CD4+CD25+ T cells with potent suppressor cell function. Blocking IDO activity with the pharmacologic inhibitor 1-methyl-D-tryptophan significantly abrogates PDC-driven inducible Treg generation and suppressor cell function. Adding kynurenine, the immediate downstream metabolite of tryptophan, bypasses the 1-methyl-D-tryptophan effect and restores PDC-driven Treg generation. Our results demonstrate that the IDO pathway is essential for PDC-driven Treg generation from CD4+ CD25- T cells and implicate the generation of kynurenine pathway metabolites as the critical mediator of this process.

Original languageEnglish (US)
Pages (from-to)5396-5404
Number of pages9
JournalJournal of Immunology
Volume181
Issue number8
DOIs
StatePublished - Jan 1 2008

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Regulatory T-Lymphocytes
Dendritic Cells
Kynurenine
T-Lymphocytes
Tryptophan
Oligodeoxyribonucleotides
HLA-DR Antigens
Up-Regulation
Ligands
Enzymes

ASJC Scopus subject areas

  • Immunology

Cite this

The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. / Chen, Wei; Liang, Xueqing; Peterson, Amanda J.; Munn, David H; Blazar, Bruce R.

In: Journal of Immunology, Vol. 181, No. 8, 01.01.2008, p. 5396-5404.

Research output: Contribution to journalArticle

Chen, Wei ; Liang, Xueqing ; Peterson, Amanda J. ; Munn, David H ; Blazar, Bruce R. / The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. In: Journal of Immunology. 2008 ; Vol. 181, No. 8. pp. 5396-5404.
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