Document Detail

Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8(+) T-cell priming capacity.
MedLine Citation:
PMID:  23278551     Owner:  NLM     Status:  MEDLINE    
Multiple endogenous mechanisms that regulate immune and inflammatory processes contribute to the maintenance of peripheral tolerance and prevent chronic inflammation in mammals. Yet pathogens and tumours are able to exploit these homeostatic pathways to foster immunosuppressive microenvironments and evade immune surveillance. The release of adenosine in the extracellular space contributes to these phenomena by exerting a broad range of immunomodulatory effects. Here we document the influence of adenosine receptor triggering on human dendritic cell differentiation and functions. We show that the expression of several immunomodulatory proteins and myeloid/monocytic lineage markers was affected by adenosine receptors and the cAMP pathway. These changes were reminiscent of the phenotype associated with tolerogenic dendritic cells and, functionally, translated into a defective capacity to prime CD8(+) T-cells with a common tumour antigen in vitro. These results establish a novel mechanism by which adenosine hampers CD8(+) T-cell immunity via dendritic cells that may contribute to peripheral tolerance as well as to the establishment of immunosuppressive microenvironments relevant to tumour biology.
John Challier; Denis Bruniquel; Andrew K Sewell; Bruno Laugel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  138     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-13     Completed Date:  2013-04-26     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  402-10     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
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MeSH Terms
Adenosine / immunology,  pharmacology*
Biological Markers / metabolism
CD8-Positive T-Lymphocytes / cytology,  drug effects*,  immunology
Cell Differentiation / drug effects
Cells, Cultured
Cyclic AMP / immunology,  pharmacology*
Cytokines / biosynthesis,  immunology
Dendritic Cells / cytology,  drug effects*,  immunology
Gene Expression / drug effects
Immunologic Factors / immunology,  pharmacology*
Monocytes / cytology,  drug effects*,  immunology
Peripheral Tolerance / drug effects
Receptors, Purinergic P1 / immunology,  metabolism
Signal Transduction / drug effects
Grant Support
BB/H001085//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Biological Markers; 0/Cytokines; 0/Immunologic Factors; 0/Receptors, Purinergic P1; E0399OZS9N/Cyclic AMP; K72T3FS567/Adenosine

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