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Adiponectin induces dendritic cell activation via PLCγ/JNK/NF-κB pathways, leading to Th1 and Th17 polarization

Authors
 Mi Young Jung  ;  Han-Soo Kim  ;  Hye-Jin Hong  ;  Byung-Soo Youn  ;  Tae Sung Kim 
Citation
 Journal of Immunology, Vol.188(6) : 2592-2601, 2012 
Journal Title
 Journal of Immunology 
ISSN
 0022-1767 
Issue Date
2012
MeSH
Adiponectin/immunology* ; Adiponectin/metabolism ; Animals ; Blotting, Western ; Cell Separation ; Dendritic Cells/immunology* ; Dendritic Cells/metabolism ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation/immunology* ; Lymphocyte Culture Test, Mixed ; MAP Kinase Signaling System/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Confocal ; NF-kappa B/immunology ; NF-kappa B/metabolism ; Phospholipase C gamma/immunology ; Phospholipase C gamma/metabolism ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/immunology* ; Th1 Cells/cytology* ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th17 Cells/cytology* ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Transfection
Keywords
Adiponectin/immunology* ; Adiponectin/metabolism ; Animals ; Blotting, Western ; Cell Separation ; Dendritic Cells/immunology* ; Dendritic Cells/metabolism ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation/immunology* ; Lymphocyte Culture Test, Mixed ; MAP Kinase Signaling System/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Confocal ; NF-kappa B/immunology ; NF-kappa B/metabolism ; Phospholipase C gamma/immunology ; Phospholipase C gamma/metabolism ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/immunology* ; Th1 Cells/cytology* ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th17 Cells/cytology* ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Transfection
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 IκB proteins, nuclear translocation of NF-κB p65 subunit, and phosphorylation of MAPKs in DCs. Pretreatment with a phospholipase C (PLC)γ inhibitor and a JNK inhibitor suppressed IL-12 production and NF-κB binding activity. Additionally, PLCγ inhibitor downregulated phosphorylation of JNK, indicating that PLCγ and JNK may be upstream molecules of NF-κB. 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-γ, whereas the blockage of IL-23 and IL-1β 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 PLCγ/JNK/NF-κB-signaling pathways, leading to enhanced Th1 and Th17 responses.
Files in This Item:
T201200695.pdf Download
DOI
22345647
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Han Soo(김한수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90849
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