title: The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.
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.
authors.affiliation: Department of Specialistic, Diagnostic, and Experimental Medicine, Institute of Hematology "Seràgnoli," University of Bologna, 40138 Bologna, Italy;
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.forename: Darina
authors.initials: D
authors.lastname: Očadlíková
authors.forename: Marilena
authors.initials: M
authors.lastname: Ciciarello
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvestrini
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lecciso
authors.forename: Camilla
authors.initials: C
authors.lastname: Jandus
authors.forename: Richard
authors.initials: R
authors.lastname: Metz
authors.forename: Cecilia
authors.initials: C
authors.lastname: Evangelisti
authors.forename: Lisa
authors.initials: L
authors.lastname: Laury-Kleintop
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
authors.forename: Antonio
authors.initials: A
authors.lastname: Curti
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D015535:Arthritis, Psoriatic / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000201:enzymology / Q000276:immunology*; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009928:Organ Specificity; D014176:Protein Biosynthesis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D013167:Spondylitis, Ankylosing / Q000276:immunology / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects; D014364:Tryptophan / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C576710:IDO1 protein, human; C576711:IDO2 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014364:Tryptophan; D015232:Dinoprostone