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The Journal of Immunology, 2002, 168: 5448-5454.
Copyright © 2002 by The American Association of Immunologists

IL-23 and IL-12 Have Overlapping, but Distinct, Effects on Murine Dendritic Cells1

Maria Laura Belladonna*, Jean-Christophe Renauld{dagger}, Roberta Bianchi*, Carmine Vacca*, Francesca Fallarino*, Ciriana Orabona*, Maria Cristina Fioretti*, Ursula Grohmann* and Paolo Puccetti2,*

* Department of Experimental Medicine, University of Perugia, Perugia, Italy; and {dagger} Ludwig Institute for Cancer Research, Brussels, Belgium

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 CD8{alpha}- and CD8{alpha}+ 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 CD8{alpha}+ 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-12R{beta}2 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.




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