title: IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells.
abstract: IL-23 is a recently discovered heterodimeric cytokine that shares biological properties with proinflammatory cytokines. The biologically active heterodimer consists of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess biological activities on T cells that are similar as well distinct from those of IL-12. We have constructed single-chain IL-23 and IL-12 fusion proteins (IL-23-Ig and IL-12-Ig) and have compared the two recombinant proteins for effects on murine dendritic cells (DC). Here we show that the IL-23-Ig can bind a significant proportion of splenic DC of both the CD8alpha(-) and CD8alpha(+) subtypes. Furthermore, IL-23and IL-12-Ig exert biological activities on DC that are only in part overlapping. While both proteins induce IL-12 production from DC, only IL-23-Ig can act directly on CD8alpha(+) DC to promote immunogenic presentation of an otherwise tolerogenic tumor peptide. In addition, the in vitro effects of IL-23-Ig did not appear to require IL-12Rbeta2 or to be mediated by the production of IL-12. These data may establish IL-23 as a novel cytokine with major effects on APC.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Belladonna
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Carmine
authors.initials: C
authors.lastname: Vacca
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Maria Cristina
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: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003713:Dendritic Cells / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D021122:Protein Subunits; D018123:Receptors, Interleukin / Q000502:physiology; D053707:Receptors, Interleukin-12; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12