Shaping immune responses through the activation of dendritic cells’ P2 receptors

Abstract

Dendritic cells (DCs) activate and shape the adaptive immune response by capturing antigens, migrating to peripheral lymphoid organs where naïve T cells reside, expressing high levels of MHC and costimulatory molecules and by secreting cytokines and chemokines. DCs are endowed with a high degree of functional plasticity and their functions are tightly regulated. Besides initiating adaptive immune responses, DCs play a key role in maintaining peripheral tolerance toward self-antigens. On the basis of the information gathered from the tissue where they reside DCs adjust their functional activity to ensure that protective immunity is favored while unwanted or exaggerated immune responses are prevented. A wide variety of signals from neighbouring cells affecting DCs functional activity have been described. Here we will discuss the complex role of extracellular nucleotides in the regulation of DCs function and the role of P2 receptors as possible tools to manipulate immune responses.

Immunoregulation through extracellular nucleotides

“…80 These effects are mimicked by the nonhydrolyzable ATP analog ATP-␥-S (an agonist of P2Y11) and by several cAMP-elevating agents, as well as by the administration of cell-permeable cAMP analogs. [80][81][82] Schnurr et al reported that P2Y11 activity inhibits IL-27 production. 83 In the same article, the authors reported the capacity of eATP to increase mRNA levels of IL-23, which potentially fosters the expansion of the proinflammatory Th17 lymphocyte subset.…”