Abstract
The IDO pathway is implicated in a number of settings which lead to acquired peripheral tolerance. One such setting may be the functional tolerance displayed by tumor-bearing hosts toward tumor-associated antigens. Foxp3 + Tregs are now recognized as a major contributor to tumor-induced immune suppression and functional tolerance. Emerging evidence links the IDO pathway with Treg biology at several points. The first is the ability of IDO-expressing DCs to drive the differentiation of naive CD4+ T cells toward a Foxp3+ (inducible Treg) phenotype. The second link is the ability of IDO-expressing DCs to directly activate mature, pre-existing Tregs for markedly enhanced suppression of target cells. And the third link is the ability of IDO to prevent the inflammation-induced conversion ("reprogramming") of Tregs into pro-inflammatory T-helper-like cells in vivo. Taken together, these findings suggest that IDO may represent an important regulatory checkpoint influencing Treg activity: both by stabilizing and augmenting the suppressive phenotype, and by preventing Treg reprogramming into non-suppressive helper-like cells.
Original language | English (US) |
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Pages (from-to) | 2240-2246 |
Number of pages | 7 |
Journal | Current Medicinal Chemistry |
Volume | 18 |
Issue number | 15 |
DOIs | |
State | Published - May 2011 |
Keywords
- Dendritic cells
- Foxp3
- IDO
- Regulatory T cells
- Tumor immunology
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Organic Chemistry