title: Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement.
abstract: In this study, using a soluble CD200-Ig fusion protein, we provide evidence that murine dendritic cells (DCs) possess a functional CD200R, whose engagement results in the reinforcement or appearance of immunosuppressive properties in these cells. In particular, the plasmacytoid subset (CD11c+B220+120G8+) of splenic DCs (pDCs) is induced by CD200-Ig to express the enzyme IDO, which initiates the tolerogenic pathway of tryptophan catabolism. As a result, pDCs are capable of suppressing Ag-specific responses in vivo when transferred into recipient hosts after treatment with CD200-Ig. IDO induction in pDCs through CD200R engagement requires type I IFNR signaling. Although the release of IFN-alpha may contribute to the full expression of CD200-Ig activity, autocrine IFN-alpha is unlikely to mediate alone the effects of CD200R engagement. These data prospect novel functions for both pDCs and the CD200-CD200R pair in the mouse. At the same time, these data underscore the possible unifying role of the IDO mechanism in immune tolerance.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Carine
authors.initials: C
authors.lastname: Asselin-Paturel
authors.forename: Carmine
authors.initials: C
authors.lastname: Vacca
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Stefania
authors.initials: S
authors.lastname: Gizzi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Fioretti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D049308:Dioxygenases; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D064446:Orexin Receptors; D010105:Oxygenases / Q000096:biosynthesis / Q000502:physiology*; D053633:Receptor, Interferon alpha-beta; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C492346:CD200 receptor, mouse; C501103:Cd200r1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D053633:Receptor, Interferon alpha-beta; D014364:Tryptophan; D010105:Oxygenases; D049308:Dioxygenases; C042739:antigens, CD200