title: Enhanced tryptophan catabolism in the absence of the molecular adapter DAP12.
abstract: DAP12 is an immunoreceptor tyrosine-based activation motif-bearing membrane adapter molecule expressed by different cell types. Although several receptors associate with DAP12 in murine dendritic cells (DC), the function of these receptors is as yet unknown. Here we report that splenic mature DC with DAP12 overexpression are characterized by an impaired tolerogenic potential. In contrast, inhibition of DAP12 function results in enhanced tolerogenesis and constitutive expression of immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO). Increased resistance to experimental encephalomyelitis is observed in DAP12 knockin mice, which is dependent on IDO expression. Therefore, DAP12-related receptors act as negative regulators of IDO-mediated tolerance in vivo.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Volpi
authors.forename: Silvia
authors.initials: S
authors.lastname: Bellocchio
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Maria C
authors.initials: MC
authors.lastname: Fioretti
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D007108:Immune Tolerance / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014364:Tryptophan / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016827:CD8 Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C484963:Tyrobp protein, mouse; D014364:Tryptophan