title: Regulation of the T Cell Response by CD39.
abstract: The ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1, or CD39) catalyzes the phosphohydrolysis of extracellular ATP (eATP) and ADP (eADP) released under conditions of inflammatory stress and cell injury. CD39 generates AMP, which is in turn used by the ecto-5'-nucleotidase CD73 to synthesize adenosine. These ectonucleotidases have a major impact on the dynamic equilibrium of proinflammatory eATP and ADP nucleotides versus immunosuppressive adenosine nucleosides. Indeed, CD39 plays a dominant role in the purinergic regulation of inflammation and the immune response because its expression is influenced by genetic and environmental factors. We review the specific role of CD39 in the kinetic regulation of cellular immune responses in the evolution of disease. We focus on the effects of CD39 on T cells and explore potential clinical applications in autoimmunity, chronic infections, and cancer.
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Maisa C
authors.initials: MC
authors.lastname: Takenaka
authors.affiliation: Divisions of Gastroenterology, Hepatology, and Transplantation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: srobson@bidmc.harvard.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Robson
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. Electronic address: fquintana@rics.bwh.harvard.edu.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D059647:Gene-Environment Interaction; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007239:Infections / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine