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Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-?B ligand (RANK)-L by rat plasmacytoid dendritic cells.

ABSTRACT: Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-?B ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4(high) pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4(low) subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system.

SUBMITTER: Anjubault T

PROVIDER: S-EPMC3302772 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-κB ligand (RANK)-L by rat plasmacytoid dendritic cells.

Anjubault Thomas T Martin Jérôme J Hubert François-Xavier FX Chauvin Camille C Heymann Dominique D Josien Régis R

PloS one 20120313 3

Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-κB ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which pla ...[more]

PMID: 22428075

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Project description:BackgroundAlkylphenols, such as nonylphenol (NP) and 4-octylphenol (4-OP), have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. Plasmacytoid dendritic cells (PDCs) can secrete large amounts of type I IFNs and are critical in immune regulation. However, there has been limited study about the influence of alkylphenols on the function of pDCs.ObjectiveThe aim of this study was to examine the effect of alkylphenols on pDC functions in vitro and in vivo and then further explored the involved signaling pathways and epigenetic changes.MethodsCirculating pDCs from human peripheral blood mononuclear cells were treated with alkylphenols with or without CpG stimulation. Alkylphenol-associated cytokine responses, signaling events, histone modifications and viral activity were further examined. In NP-exposed mice, the effect of NP on splenic pDC function and allergic lung inflammation were also assessed.ResultsThe results showed that NP increased the expression of TNF-?, but suppressed IL-10 production in the range of physiological doses, concomitant with activation of the MKK3/6-p38 signaling pathway and enhanced levels of acetylated histone 3 as well as histone 4 at the TNFA gene locus. Further, in CpG-stimulated pDCs, NP suppressed type I IFNs production, associated with down-regulation of IRF-7 and MKK1/2-ERK-Elk-1 pathways and led to the impaired anti-enterovirus 71 activity in vitro. Additionally, splenic pDCs from NP-exposed mice showed similar cytokine changes upon CpG stimulation under conditions relevant to route and level of exposure in humans. NP treatment also enhanced allergic lung inflammation in vivo.ConclusionAlkylphenols may influence pDCs' functions via their abilities to induce expression of a pro-inflammatory cytokine, TNF-?, and to suppress regulatory cytokines, including IL-10, IFN-? and IFN-?, suggesting the potential impact of endocrine disrupting chemicals on immune regulation.

Dataset Information

Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-?B ligand (RANK)-L by rat plasmacytoid dendritic cells.

Publications

Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-κB ligand (RANK)-L by rat plasmacytoid dendritic cells.

Similar Datasets

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