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

Mi Young Jung, Han Soo Kim, Hye Jin Hong, Byung Soo Youn, Tae Sung Kim

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 IkB 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.

Original languageEnglish
Pages (from-to)2592-2601
Number of pages10
JournalJournal of Immunology
Volume188
Issue number6
DOIs
Publication statusPublished - 2012 Mar 15

Fingerprint

Adiponectin
Type C Phospholipases
Dendritic Cells
Interleukin-12
Phosphorylation
Interleukin-23
Th17 Cells
Th1 Cells
Interleukin-17
Protein Transport
Coculture Techniques
Interleukin-1
Immunization
Down-Regulation
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Adiponectin induces dendritic cell activation via PLCγ/JNK/NF- κB pathways, leading to Th1 and Th17 polarization. / Jung, Mi Young; Kim, Han Soo; Hong, Hye Jin; Youn, Byung Soo; Kim, Tae Sung.

In: Journal of Immunology, Vol. 188, No. 6, 15.03.2012, p. 2592-2601.

Research output: Contribution to journalArticle

Jung, Mi Young ; Kim, Han Soo ; Hong, Hye Jin ; Youn, Byung Soo ; Kim, Tae Sung. / Adiponectin induces dendritic cell activation via PLCγ/JNK/NF- κB pathways, leading to Th1 and Th17 polarization. In: Journal of Immunology. 2012 ; Vol. 188, No. 6. pp. 2592-2601.
@article{92e3df61a10c4feda05c81bfa9275605,
title = "Adiponectin induces dendritic cell activation via PLCγ/JNK/NF- κB 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 IkB 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.",
author = "Jung, {Mi Young} and Kim, {Han Soo} and Hong, {Hye Jin} and Youn, {Byung Soo} and Kim, {Tae Sung}",
year = "2012",
month = "3",
day = "15",
doi = "10.4049/jimmunol.1102588",
language = "English",
volume = "188",
pages = "2592--2601",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Adiponectin induces dendritic cell activation via PLCγ/JNK/NF- κB pathways, leading to Th1 and Th17 polarization

AU - Jung, Mi Young

AU - Kim, Han Soo

AU - Hong, Hye Jin

AU - Youn, Byung Soo

AU - Kim, Tae Sung

PY - 2012/3/15

Y1 - 2012/3/15

N2 - 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 IkB 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.

AB - 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 IkB 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.

UR - http://www.scopus.com/inward/record.url?scp=84863295568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863295568&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1102588

DO - 10.4049/jimmunol.1102588

M3 - Article

C2 - 22345647

AN - SCOPUS:84863295568

VL - 188

SP - 2592

EP - 2601

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -