The P2X7 Receptor in Infection and Inflammation

• Published in: Immunity (Cambridge, Mass.) Mass.), 2017-07, Vol.47 (1), p.15-31
• Main Authors: Di Virgilio, Francesco, Dal Ben, Diego, Sarti, Alba Clara, Giuliani, Anna Lisa, Falzoni, Simonetta
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adenosine triphosphate; Alternative splicing; Animals; ATP; Cancer; Cell activation; Cell death; Cell Differentiation; Differentiation; Haplotypes; Humans; Immune system; Immunity; Infection - drug therapy; Infection - immunology; Infections; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Ligands; Lymphocytes; Macrophages - immunology; Metabolism; Neutrophils; Proteins; Purine P2 receptors; Purinergic P2X Receptor Agonists - therapeutic use; Receptors; Receptors, Purinergic P2X7 - immunology; Receptors, Purinergic P2X7 - metabolism; Signal transduction; Single-nucleotide polymorphism; T-Lymphocytes - immunology; Transcription activation; Transduction
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2017.06.020

Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. However, an in-depth knowledge of its structure and of the associated signal transduction mechanisms is needed for an effective therapeutic development. Extracellular ATP is a common constitutent of the inflammatory milieu, where it modulates immune cell responses by activating a family of plasma membrane receptors named P2. In this review, Di Virgilio et al. discuss the central role played by the P2X7 receptor in promoting inflammation and driving innate and adaptive immunity.