| First Author | Jung MY | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 12 | Pages | 6848-59 |
| PubMed ID | 21551364 | Mgi Jnum | J:175497 |
| Mgi Id | MGI:5285806 | Doi | 10.4049/jimmunol.1003996 |
| Citation | Jung MY, et al. (2011) IL-32gamma induces the maturation of dendritic cells with Th1- and Th17-polarizing ability through enhanced IL-12 and IL-6 production. J Immunol 186(12):6848-59 |
| abstractText | IL-32, a newly described multifunctional cytokine, has been associated with a variety of inflammatory diseases, including rheumatoid arthritis, vasculitis, and Crohn's disease. In this study, we investigated the immunomodulatory effects of IL-32gamma on bone marrow-derived dendritic cell (DC)-driven Th responses and analyzed the underlying signaling events. IL-32gamma-treated DCs exhibited upregulated expression of cell-surface molecules and proinflammatory cytokines associated with DC maturation and activation. In particular, IL-32gamma treatment significantly increased production of IL-12 and IL-6 in DCs, which are known as Th1- and Th17-polarizing cytokines, respectively. This increased production was inhibited by the addition of specific inhibitors of the activities of phospholipase C (PLC), JNK, and NF-kappaB. IL-32gamma treatment increased the phosphorylation of JNK and the degradation of both IkappaBalpha and IkappaBbeta in DCs, as well as NF-kappaB binding activity to the kappaB site. The PLC inhibitor suppressed NF-kappaB DNA binding activity and JNK phosphorylation increased by IL-32gamma treatment, thereby indicating that IL-32gamma induced IL-12 and IL-6 production in DCs via a PLC/JNK/NF-kappaB signaling pathway. Importantly, IL-32gamma-stimulated DCs significantly induced both Th1 and Th17 responses when cocultured with CD4(+) T cells. The addition of a neutralizing anti-IL-12 mAb abolished the secretion of IFN-gamma in a dose-dependent manner; additionally, the blockage of IL-1beta and IL-6, but not of IL-21 or IL-23p19, profoundly inhibited IL-32gamma-induced IL-17 production. These results demonstrated that IL-32gamma could effectively induce the maturation and activation of immature DCs, leading to enhanced Th1 and Th17 responses as the result of increased IL-12 and IL-6 production in DCs. |
