Adiponectin Induces Dendritic Cell Activation via PLC gamma/JNK/NF-kappa B Pathways, Leading to Th1 and Th17 Polarization

Abstract

Adiponectin (APN) is a crucial regulator for many inflammatory processes, but its effect on Th cell-mediated responses has not been fully understood. Thus, we investigated the immune-modulatory effects of APN on dendritic cells (DCs) controlling Th cell polarization. APN induced maturation and activation of DCs, as demonstrated by the increased expression of MHC class II, costimulatory molecules in both mouse and human DCs, and it significantly enhanced production of proinflammatory cytokines. APN triggered degradation of I kappa B proteins, nuclear translocation of NF-kappa B p65 subunit, and phosphorylation of MAPKs in DCs. Pretreatment with a phospholipase C (PLC)gamma inhibitor and a JNK inhibitor suppressed IL-12 production and NF-kappa B binding activity. Additionally, PLC gamma inhibitor downregulated phosphorylation of JNK, indicating that PLC gamma and JNK may be upstream molecules of NF-kappa B. Importantly, APN-treated DCs significantly induced both Th1 and Th17 responses in allogeneic CD4(+) T cells. The addition of a neutralizing anti-IL-12 mAb to the cocultures abolished the secretion of IFN-gamma, whereas the blockage of IL-23 and IL-1 beta suppressed APN-induced IL-17 production. Immunization of mice with OVA-pulsed, APN-treated DCs efficiently led to Ag-specific Th1 and Th17 cell responses. Taken together, these results demonstrated that APN effectively induced activation of DCs through PLC gamma/JNK/NF-kappa B-signaling pathways, leading to enhanced Th1 and Th17 responses. The Journal of Immunology, 2012, 188: 2592-2601.