IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells.
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.
Belladonna
Maria Laura
ML
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Renauld
Jean-Christophe
JC
Bianchi
Roberta
R
Vacca
Carmine
C
Fallarino
Francesca
F
Orabona
Ciriana
C
Fioretti
Maria Cristina
MC
Grohmann
Ursula
U
Puccetti
Paolo
P
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
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