Document Detail


Protease-activated receptor-2 signalling by tissue factor on dendritic cells suppresses antigen-specific CD4+ T-cell priming.
MedLine Citation:
PMID:  23347132     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The precise function of tissue factor (TF) expressed by dendritic cells (DC) is uncertain. As well as initiating thrombin generation it can signal through protease-activated receptor 2 (PAR-2) when complexed with factor VIIa. We investigated the expression and function of TF on mouse bone marrow (BM) -derived DC; 20% of BM-derived DC expressed TF, which did not vary after incubation with lipopolysaccharide (LPS) or dexamethasone (DEX). However, the pro-coagulant activity of DEX-treated DC in recalcified plasma was 30-fold less than LPS-treated DC. In antigen-specific and allogeneic T-cell culture experiments, the TF on DEX-treated DC provided a signal through PAR-2, which contributed to the reduced ability of these cells to stimulate CD4(+) T-cell proliferation and cytokine production. In vivo, an inhibitory anti-TF antibody and a PAR-2 antagonist enhanced antigen-specific priming in two models where antigen was given without adjuvant, with an effect approximately 50% that seen with LPS, suggesting that a similar mechanism was operational physiologically. These data suggest a novel TF and PAR-2-dependent mechanism on DEX-DC in vitro and unprimed DC in vivo that contributes to the low immunogenicity of these cells. Targeting this pathway has the potential to influence antigen-specific CD4(+) T-cell activation.
Authors:
Seema Shrivastava; Liang Ma; El-Li Tham; John H McVey; Daxin Chen; Anthony Dorling
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-07-01     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  219-26     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology,  pharmacology
Antigens / immunology
Bone Marrow Cells / drug effects,  immunology*,  metabolism
CD4-Positive T-Lymphocytes / drug effects,  immunology*,  metabolism
Cell Proliferation / drug effects
Cells, Cultured
Cytokines / immunology,  metabolism
Dendritic Cells / drug effects,  immunology*,  metabolism
Dexamethasone / pharmacology
Flow Cytometry
Lipopolysaccharides / pharmacology
Lymphocyte Activation / drug effects,  immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Receptor, PAR-2 / antagonists & inhibitors,  immunology*,  metabolism
Signal Transduction / drug effects,  immunology*
Thromboplastin / immunology*,  metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
G0401591//Medical Research Council; G0801965//Medical Research Council; MR/J006742/1//Medical Research Council; //British Heart Foundation
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens; 0/Cytokines; 0/Lipopolysaccharides; 0/Receptor, PAR-2; 7S5I7G3JQL/Dexamethasone; 9035-58-9/Thromboplastin
Comments/Corrections

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