IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells

被引:205
作者
Belladonna, ML
Renauld, JC
Bianchi, R
Vacca, C
Fallarino, F
Orabona, C
Fioretti, MC
Grohmann, U
Puccetti, P
机构
[1] Univ Perugia, Pharmacol Sect, Dept Expt Med, I-06126 Perugia, Italy
[2] Ludwig Inst Canc Res, Brussels, Belgium
关键词
D O I
10.4049/jimmunol.168.11.5448
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-23-and 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 CD8a+ 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.
引用
收藏
页码:5448 / 5454
页数:7
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