IL-27 Acts on DCs to Suppress the T Cell Response and Autoimmunity by Inducing Expression of the Immunoregulatory Molecule CD39

Nat Immunol. 2013 Oct;14(10):1054-63. doi: 10.1038/ni.2695. Epub 2013 Sep 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Apyrase / genetics*
  • Apyrase / metabolism
  • Autoantibodies / immunology
  • Autoimmunity* / drug effects
  • Carrier Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Expression
  • Gene Expression Regulation / drug effects
  • Immune Tolerance / immunology
  • Interleukin-17 / pharmacology*
  • Mice
  • Mice, Knockout
  • Myelin Sheath / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • Transcription, Genetic / drug effects

Substances

  • Antibodies
  • Antigens, CD
  • Autoantibodies
  • Carrier Proteins
  • Cytokines
  • Il27ra protein, mouse
  • Interleukin-17
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, Cytokine
  • Apyrase
  • CD39 antigen

Associated data

  • GEO/GSE49328