The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells

Jeffrey M. Wilson, William G. Ross, Oma Agbai, Renea Frazier, Robert A. Figler, Jayson Rieger, Joel Linden, Peter B. Ernst

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4+ T cell responses. While adenosine clearly has direct effects on CD4+ T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5′-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-α and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4 + T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A2A adenosine receptor (A2AAR) and A2BAR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A2AAR-/- and A 2BAR-/-mice, it was shown that NECA modulates TNF-α, IL-12, IL-10, and CD86 responses predominantly via A2BAR. These data indicate that engagement of A2BAR modifies murine BMDC maturation and suggest that adenosine regulates CD4+ T cell responses by selecting for DC with impaired immunogencity.

Original languageEnglish (US)
Pages (from-to)4616-4623
Number of pages8
JournalJournal of Immunology
Volume182
Issue number8
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

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Adenosine A2B Receptors
Adenosine-5'-(N-ethylcarboxamide)
Dendritic Cells
Adenosine
Adenosine A2A Receptors
T-Lymphocytes
Purinergic P1 Receptors
Interleukin-12
Interleukin-10
Purinergic P1 Receptor Agonists
Purine Nucleosides
Interleukin-2
Real-Time Polymerase Chain Reaction
Anti-Inflammatory Agents
Cell Proliferation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Wilson, J. M., Ross, W. G., Agbai, O., Frazier, R., Figler, R. A., Rieger, J., ... Ernst, P. B. (2009). The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. Journal of Immunology, 182(8), 4616-4623. https://doi.org/10.4049/jimmunol.0801279

The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. / Wilson, Jeffrey M.; Ross, William G.; Agbai, Oma; Frazier, Renea; Figler, Robert A.; Rieger, Jayson; Linden, Joel; Ernst, Peter B.

In: Journal of Immunology, Vol. 182, No. 8, 15.04.2009, p. 4616-4623.

Research output: Contribution to journalArticle

Wilson, JM, Ross, WG, Agbai, O, Frazier, R, Figler, RA, Rieger, J, Linden, J & Ernst, PB 2009, 'The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells', Journal of Immunology, vol. 182, no. 8, pp. 4616-4623. https://doi.org/10.4049/jimmunol.0801279
Wilson, Jeffrey M. ; Ross, William G. ; Agbai, Oma ; Frazier, Renea ; Figler, Robert A. ; Rieger, Jayson ; Linden, Joel ; Ernst, Peter B. / The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. In: Journal of Immunology. 2009 ; Vol. 182, No. 8. pp. 4616-4623.
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