P2X receptors in immune cells: key regulators of inflammation and immune function

P2X receptors are a family of ATP-gated ion channels comprising seven subtypes (P2X1-P2X7). These receptors mediate rapid cation fluxes and downstream signaling events that regulate inflammation, synaptic transmission, and cell death. P2X receptors are widely expressed in immune cells of both myeloid and lymphoid lineages, including macrophages, microglia, dendritic cells, neutrophils, eosinophils, natural killer cells, myeloid-derived suppressor cells, T, B, and innate lymphocytes. Through these diverse populations, P2X receptors influence cytokine secretion, chemotaxis, phagocytosis, antigen presentation, and the balance between immune activation and suppression. Beyond initiating inflammatory responses to infectious or sterile insults, P2X signaling contributes to immune tolerance and homeostasis. This review summarizes current and emerging insights into the immunomodulatory roles of P2X receptors across innate and adaptive compartments, highlighting mechanistic pathways and translational relevance. Collectively, P2X receptors act as central integrators of metabolic and inflammatory cues, representing promising therapeutic targets for inflammatory, autoimmune, and neuroimmune diseases, as well as cancer.