title: Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent dendritic cells.
abstract: CD8(-) and CD8(+) dendritic cells (DCs) are distinct subsets of mouse splenic accessory cells with opposite but flexible programs of Ag presentation, leading to immunogenic and tolerogenic responses, respectively. In this study, we show that the default tolerogenic function of CD8(+) DCs relies on autocrine TGF-beta, which sustains the activation of IDO in response to environmental stimuli. CD8(-) DCs do not produce TGF-beta, yet externally added TGF-beta induces IDO and turns those cells from immunogenic into tolerogenic cells. The acquisition of a suppressive phenotype by CD8(-) DCs correlates with activation of the PI3K/Akt and noncanonical NF-kappaB pathways. These data are the first to link TGF-beta signaling with IDO in controlling spontaneous tolerogenesis by DCs.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy. laurabell@tin.it
authors.forename: Maria L
authors.initials: ML
authors.lastname: Belladonna
authors.forename: Claudia
authors.initials: C
authors.lastname: Volpi
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Carmine
authors.initials: C
authors.lastname: Vacca
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Maria T
authors.initials: MT
authors.lastname: Pallotta
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Stefania
authors.initials: S
authors.lastname: Gizzi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Fioretti
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D016827:CD8 Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt