Modulation of innate and adaptive immunity by P2X ion channels

Extracellular ATP is a major component of the inflammatory microenvironment where it accumulates following cell and tissue injury but also as a consequence of non-lytic release from activated inflammatory cells. In the inflammatory microenvironment ATP binds and activates nucleotide receptors of the P2Y and P2X subfamilies expressed by immune cells. P2Y receptors are G-protein-coupled, while P2X receptors are cation-selective channels. Changes in the intracellular ion homeostasis triggered by P2X receptor stimulation trigger multiple key responses crucial for initiation, propagation, and resolution of inflammation. In the P2X receptor family, the P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses. Although clinical studies have been so far rather inconclusive, it is believed that P2X7 receptor targeting might offer novel perspectives for anti-inflammatory therapy.