The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.

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Serval ID
serval:BIB_0FE586F092BC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.
Journal
Journal of Immunology
Author(s)
Trabanelli S., Očadlíková D., Ciciarello M., Salvestrini V., Lecciso M., Jandus C., Metz R., Evangelisti C., Laury-Kleintop L., Romero P., Prendergast G.C., Curti A., Lemoli R.M.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
192
Number
3
Pages
1231-1240
Language
english
Abstract
Dendritic cells (DCs) are professional APCs that have a role in the initiation of adaptive immune responses and tolerance. Among the tolerogenic mechanisms, the expression of the enzyme IDO1 represents an effective tool to generate T regulatory cells. In humans, different DC subsets express IDO1, but less is known about the IDO1-related enzyme IDO2. In this study, we found a different pattern of expression and regulation between IDO1 and IDO2 in human circulating DCs. At the protein level, IDO1 is expressed only in circulating myeloid DCs (mDCs) and is modulated by PGE2, whereas IDO2 is expressed in both mDCs and plasmacytoid DCs and is not modulated by PGE2. In healthy subjects, IDO1 expression requires the presence of PGE2 and needs continuous transcription and translation, whereas IDO2 expression is constitutive, independent from suppressor of cytokine signaling 3 activity. Conversely, in patients suffering from inflammatory arthritis, circulating DCs express both IDO1 and IDO2. At the functional level, both mDCs and plasmacytoid DCs generate T regulatory cells through an IDO1/IDO2-dependent mechanism. We conclude that, in humans, whereas IDO1 provides an additional mechanism of tolerance induced by proinflammatory mediators, IDO2 is stably expressed in steady-state conditions and may contribute to the homeostatic tolerogenic capacity of DCs.
Keywords
Arthritis, Psoriatic/immunology, Arthritis, Psoriatic/pathology, Arthritis, Rheumatoid/immunology, Arthritis, Rheumatoid/pathology, Cells, Cultured, Dendritic Cells/classification, Dendritic Cells/enzymology, Dinoprostone/pharmacology, Dinoprostone/physiology, Enzyme Induction/drug effects, Homeostasis, Humans, Immune Tolerance, Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis, Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics, Monocytes/cytology, Monocytes/drug effects, Organ Specificity, Protein Biosynthesis/drug effects, RNA Interference, RNA, Small Interfering/pharmacology, Spondylitis, Ankylosing/immunology, Spondylitis, Ankylosing/pathology, Suppressor of Cytokine Signaling Proteins/antagonists & inhibitors, T-Lymphocytes, Regulatory/immunology, Transcription, Genetic/drug effects, Tryptophan/metabolism, Up-Regulation/drug effects
Pubmed
Create date
27/10/2014 15:09
Last modification date
20/08/2019 12:36
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