title: 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-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.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Carla
authors.initials: C
authors.lastname: Lippens
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Fernanda V
authors.initials: FV
authors.lastname: Duraes
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Dubrot
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Dale
authors.initials: D
authors.lastname: Brighouse
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lacroix
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Magali
authors.initials: M
authors.lastname: Irla
authors.affiliation: Flow Cytometry Core Facility, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aubry-Lachainaye
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Mandl
authors.affiliation: Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: stephanie.hugues@unige.ch.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hugues
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: Antigen presentation; Experimental autoimmune encephalomyelitis; Indoleamine 2,3-dyoxygenase; Plasmacytoid dendritic cells; Regulatory T cells; Tolerance