Engagement of the A2B adenosine receptor modifies murine DC maturation

Abstract

Background: Adenosine exerts anti‐inflammatory effects on most immune and inflammatory cells, including the cytokine response of dendritic cells (DC). It is not clear which adenosine receptors mediate this response or whether adenosine affects other aspects of DC maturation. Methods: Cytokine production and co‐stimulatory marker expression were assayed in murine bone marrow‐derived DCs (BMDC) primed with LPS in the presence or absence of the non‐selective adenosine agonist NECA. Responses were compared in BMDCs from WT or adenosine receptor knock‐out mice, or with adenosine receptor subtype selective antagonists. Results: NECA inhibited TNF‐α and IL‐12 protein in a concentration dependent manner, whereas IL‐10 production was increased. NECA significantly impaired CD86 expression compared to vehicle control as measured by mean fluorescence (p <0.05). The A2A adenosine receptor (A2AAR) and A2BAR were found to be the predominant adenosine receptors expressed in BMDCs by real‐time RT‐PCR assessment of mRNA transcripts. Using adenosine receptor subtype selective antagonists and BMDCs derived from A2AAR−/−and A2BAR−/−mice, it was shown that NECA modulation of TNF‐α, IL‐12, IL‐10, and CD86 responses require A2BAR. Conclusions: These data indicate that engagement of A2BAR impairs murine BMDC maturation, and suggest that adenosine may favor tolerance through actions on DCs.