P2X7 Receptor at the Crossroads of T Cell Fate

Int J Mol Sci. 2020 Jul 13;21(14):4937. doi: 10.3390/ijms21144937.

Abstract

The P2X7 receptor is a ligand-gated, cation-selective channel whose main physiological ligand is ATP. P2X7 receptor activation may also be triggered by ARTC2.2-dependent ADP ribosylation in the presence of extracellular NAD. Upon activation, this receptor induces several responses, including the influx of calcium and sodium ions, phosphatidylserine externalization, the formation of a non-selective membrane pore, and ultimately cell death. P2X7 receptor activation depends on the availability of extracellular nucleotides, whose concentrations are regulated by the action of extracellular nucleotidases such as CD39 and CD38. The P2X7 receptor has been extensively studied in the context of the immune response, and it has been reported to be involved in inflammasome activation, cytokine production, and the migration of different innate immune cells in response to ATP. In adaptive immune responses, the P2X7 receptor has been linked to T cell activation, differentiation, and apoptosis induction. In this review, we will discuss the evidence of the role of the P2X7 receptor on T cell differentiation and in the control of T cell responses in inflammatory conditions.

Keywords: P2X7 receptor; T cell; ectonucleotidases.

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / physiology
  • Adenosine Triphosphate / physiology
  • Animals
  • Antigens, CD / physiology
  • Apoptosis / physiology
  • Apyrase / physiology
  • Cell Differentiation / physiology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Inflammasomes / metabolism
  • Ion Channel Gating / physiology
  • Lymphocyte Activation / physiology
  • Mice
  • Nucleotides / metabolism
  • Phosphatidylserines / metabolism
  • Rats
  • Receptors, Purinergic P2X7 / chemistry
  • Receptors, Purinergic P2X7 / drug effects
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / physiology*
  • Signal Transduction / physiology
  • Structure-Activity Relationship
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, CD
  • Inflammasomes
  • Nucleotides
  • Phosphatidylserines
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • ADP-ribosyl Cyclase 1
  • Apyrase
  • CD39 antigen