P2 Receptors: Novel Disease Markers and Metabolic Checkpoints in Immune Cells

Extracellular ATP (eATP) and P2 receptors are novel emerging regulators of T-lymphocyte responses. Cellular ATP is released via multiple pathways and accumulates at sites of tissue damage and inflammation. P2 receptor expression and function are affected by numerous single nucleotide polymorphisms (SNPs) associated with diverse disease conditions. Stimulation by released nucleotides (purinergic signalling) modulates several T-lymphocyte functions, among which energy metabolism. Energy metabolism, whether oxidative or glycolytic, in turn deeply affects T-cell activation, differentiation and effector responses. Specific P2R subtypes, among which the P2X7 receptor (P2X7R), are either up- or down-regulated during T-cell activation and differentiation; thus, they can be considered indexes of activation/quiescence, reporters of T-cell metabolic status and, in principle, markers of immune-mediated disease conditions.