Document Detail

IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39.
MedLine Citation:
PMID:  23995234     Owner:  NLM     Status:  MEDLINE    
Dendritic cells (DCs) control the balance between effector T cells and regulatory T cells in vivo. Hence, the study of DCs might identify mechanisms of disease pathogenesis and guide new therapeutic approaches for disorders mediated by the immune system. We found that interleukin 27 (IL-27) signaling in mouse DCs limited the generation of effector cells of the TH1 and TH17 subsets of helper T cells and the development of experimental autoimmune encephalomyelitis (EAE). The effects of IL-27 were mediated at least in part through induction of the immunoregulatory molecule CD39 in DCs. IL-27-induced CD39 decreased the extracellular concentration of ATP and downregulated nucleotide-dependent activation of the NLRP3 inflammasome. Finally, therapeutic vaccination with IL-27-conditioned DCs suppressed established relapsing-remitting EAE. Thus, IL-27 signaling in DCs limited pathogenic T cell responses and the development of autoimmunity.
Ivan D Mascanfroni; Ada Yeste; Silvio M Vieira; Evan J Burns; Bonny Patel; Ido Sloma; Yan Wu; Lior Mayo; Rotem Ben-Hamo; Sol Efroni; Vijay K Kuchroo; Simon C Robson; Francisco J Quintana
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-09-01
Journal Detail:
Title:  Nature immunology     Volume:  14     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-19     Completed Date:  2013-11-15     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1054-63     Citation Subset:  IM    
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MeSH Terms
Antibodies / immunology
Antigen Presentation / drug effects,  immunology
Antigens, CD / genetics*,  metabolism
Apyrase / genetics*,  metabolism
Autoantibodies / immunology
Autoimmunity* / drug effects
Carrier Proteins / metabolism
Cell Differentiation / genetics,  immunology
Cells, Cultured
Cytokines / biosynthesis
Dendritic Cells / drug effects*,  immunology*,  metabolism
Encephalomyelitis, Autoimmune, Experimental / genetics,  immunology
Gene Expression
Gene Expression Regulation / drug effects
Immune Tolerance / immunology
Interleukin-17 / pharmacology*
Mice, Knockout
Myelin Sheath / immunology
Receptors, Cytokine / genetics,  metabolism
Signal Transduction
T-Lymphocyte Subsets / cytology,  drug effects*,  immunology*
Transcription, Genetic / drug effects
Grant Support
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD; 0/Autoantibodies; 0/CIAS1 protein, mouse; 0/Carrier Proteins; 0/Cytokines; 0/Il27ra protein, mouse; 0/Interleukin-17; 0/Receptors, Cytokine; EC; EC antigen

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