IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity

Abstract Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine...

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Bibliographic Details
Published in:Journal of autoimmunity 2016-12, Vol.75, p.39-49
Main Authors: Lippens, Carla, Duraes, Fernanda V, Dubrot, Juan, Brighouse, Dale, Lacroix, Mathilde, Irla, Magali, Aubry-Lachainaye, Jean-Pierre, Reith, Walter, Mandl, Judith N, Hugues, Stéphanie
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Antigen presentation
Autoimmunity - genetics
Autoimmunity - immunology
Cells, Cultured
Coculture Techniques
Dendritic Cells - immunology
Dendritic Cells - metabolism
Encephalomyelitis, Autoimmune, Experimental - enzymology
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology
Experimental autoimmune encephalomyelitis
Flow Cytometry
Gene Expression Regulation, Enzymologic
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - metabolism
Humans
Immunology
Indoleamine 2,3-dyoxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Life Sciences
Lymph Nodes - enzymology
Lymph Nodes - immunology
Mice, Inbred C57BL
Mice, Transgenic
Plasmacytoid dendritic cells
Regulatory T cells
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Tolerance
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Summary:Abstract Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine-2,3-dioxygenase (IDO) in steady-state lymph nodes (LNs). IDO expression by LN pDCs was closely dependent on MHCII-mediated, antigen-dependent, interactions with Treg. We further established that IDO production by pDCs was necessary to confer suppressive function to Tregs. During EAE development, IDO expression by pDCs was required for the generation of Tregs capable of dampening the priming of encephalitogenic T cell and disease severity. Thus, we describe a novel crosstalk between pDCs and Tregs: Tregs shape tolerogenic functions of pDCs prior to inflammation, such that pDCs in turn, promote Treg suppressive functions during autoimmunity.
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2016.07.004