P2Y receptors in dendritic cells: from inflammation to tolerance

Abstract

AbstractExtracellular nucleotides released in the context of immune and inflammatory responses regulate all components of dendritic cell (DC) function: chemotaxis, antigen uptake, expression of costimulatory molecules, and cytokine secretion. Furthermore, mainly using gene expression profiling, we identified a large number of ATP target genes in human DCs that could play a role in tolerance and tumor development. We have now integrated these findings and related publications in a nonexhaustive review of the wide action of ATP on DCs. ATP, which was previously considered as a danger signal, is also a potent regulator of immunosuppressive and tolerogenic proteins such as thrombospondin‐1 and indoleamine 2′,3′‐dioxygenase. ATP induces a semimaturation state of DCs that can be associated with immune tolerance by regulating costimulatory molecules and cytokine/chemokine expression profiles. Immune tolerance could thus be initiated at the level of DCs. These actions are mediated by the P2Y11 receptor and P2Y11 agonists could thus be used to generate tolerogenic DCs and as useful tools for DC‐based immunotherapies. ATP released from tumor cells can have a tumorigenic action through the generation of semimature tolerogenic DCs and the secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) and amphiregulin from DCs. Antagonists of ATP receptors expressed on DCs and antibodies blocking ATP target genes could have a therapeutic potential by acting as antitumor agents. WIREs Membr Transp Signal 2013, 2:37–42. doi: 10.1002/wmts.75For further resources related to this article, please visit the WIREs website.