The IL-12 family of heterodimeric cytokines， consisting of IL-12， IL-23， IL-27， and IL-35， has important roles in regulating the immune response. IL-12 family members are comprised of a heterodimer consisting of α and β chains: IL-12 (p40 and p35)， IL-23 (p40 and p19)， IL-27 (Ebi3 and p28)， and IL-35 (Ebi3 and p35). Given the combinatorial nature of the IL-12 family， we generated adenoviral vectors expressing two putative IL-12 family members not yet found naturally， termed IL-X (Ebi3 and p19) and IL-Y (p40 and p28)， as single-chain molecules. Single chain IL-Y (scIL-Y)， but not scIL-X， was able to stimulate significantly a unique cytokine/chemokine expression profile as well as acti... More
The IL-12 family of heterodimeric cytokines， consisting of IL-12， IL-23， IL-27， and IL-35， has important roles in regulating the immune response. IL-12 family members are comprised of a heterodimer consisting of α and β chains: IL-12 (p40 and p35)， IL-23 (p40 and p19)， IL-27 (Ebi3 and p28)， and IL-35 (Ebi3 and p35). Given the combinatorial nature of the IL-12 family， we generated adenoviral vectors expressing two putative IL-12 family members not yet found naturally， termed IL-X (Ebi3 and p19) and IL-Y (p40 and p28)， as single-chain molecules. Single chain IL-Y (scIL-Y)， but not scIL-X， was able to stimulate significantly a unique cytokine/chemokine expression profile as well as activate STAT3 in mice， in part， through a pathway involving IL-27Rα in splenocytes. Adenoviral-mediated， intratumoral delivery of scIL-Y increased tumor growth in contrast to the anti-tumor effects of scIL-12 and scIL-23. Similarly， treatment of prediabetic NOD mice by intravenous injection of Ad.scIL-Y prevented the onset of hyperglycemia. Analysis of cells from Ad.scIL-Y-treated NOD mice demonstrated that scIL-Y reduced expression of inflammatory mediators such as IFN-γ. Our data demonstrate that a novel， synthetic member of the IL-12 family， termed IL-Y， confers unique immunosuppressive effects in two different disease models and thus could have therapeutic applications.
