Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP

• Published in: The Journal of immunology (1950) 2010-11, Vol.185 (10), p.5900-5906
• Main Authors: Ben Addi, Abduelhakem, Cammarata, Dorothée, Conley, Pamela B, Boeynaems, Jean-Marie, Robaye, Bernard
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - analogs & derivatives; Adenosine Diphosphate - immunology; Adenosine Diphosphate - metabolism; Animals; Antigen Presentation - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Endocytosis - immunology; Humans; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Purinergic P2Y12 - immunology; Receptors, Purinergic P2Y12 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; Thionucleotides - immunology; Thionucleotides - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0901799

The effects of ADP on the biology of dendritic cells have been studied much less than those of ATP or adenosine. In this study, we showed that adenosine-5'-O-(2-thiodiphosphate) (ADPβS) induced intracellular Ca(2+) transients in murine dendritic cells (DCs). This effect was abolished by AR-C69931MX, a dual P2Y(12) and P2Y(13) receptor antagonist. RT-PCR experiments revealed the expression of both P2Y(12) and P2Y(13) mRNA in DCs. The Ca(2+) response to ADPβS was maintained in P2Y(13)-deficient DCs, whereas it was abolished completely in P2Y(12)(-/-) DCs. ADPβS stimulated FITC-dextran and OVA capture in murine DCs through macropinocytosis, and this effect was abolished in P2Y(12)(-/-) DCs. ADPβS had a similar effect on FITC-dextran uptake by human monocyte-derived DCs. OVA loading in the presence of ADPβS increased the capacity of DCs to stimulate OVA-specific T cells, whereas ADPβS had no effect on the ability of DCs to stimulate allogeneic T cells. Moreover, after immunization against OVA, the serum level of anti-OVA IgG1 was significantly lower in P2Y(12)(-/-) mice than that in wild-type controls. In conclusion, we have shown that the P2Y(12) receptor is expressed in murine DCs and that its activation increased Ag endocytosis by DCs with subsequent enhancement of specific T cell activation.