Regulation of the T Cell Response by CD39

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...

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Vydáno v:Trends in immunology Ročník 37; číslo 7; s. 427 - 439
Hlavní autoři: Takenaka, Maisa C., Robson, Simon, Quintana, Francisco J.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Elsevier Ltd 01.07.2016
Elsevier Limited
Témata:
5'-Nucleotidase - metabolism
Adenosine
Adenosine - metabolism
Adenosine Monophosphate - metabolism
Allergy and Immunology
Animals
Antigens, CD - metabolism
Apoptosis
Apyrase - metabolism
Autoimmune Diseases - immunology
Autoimmunity
Dendritic cells
Enzymes
Gene-Environment Interaction
Humans
Immune Tolerance - immunology
Infection - immunology
Infections
Inflammation - immunology
Kinases
Lymphocyte Activation
Lymphocytes
Medical research
Metabolism
Metabolites
Neoplasms - immunology
Neutrophils
Proteins
T-Lymphocytes - immunology
ISSN:1471-4906, 1471-4981, 1471-4981
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Shrnutí: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. CD39 regulates T cell activation, polarization, and stability by scavenging immunostimulatory extracellular ATP (eATP) and promoting the generation of immunosuppressive adenosine. CD39 impacts T cell response by acting directly on T cells, and also indirectly by modulating the activity of antigen-presenting cells. The regulation of CD39 expression by cytokines and other immunological stimuli modulates the immune response in the context of inflammation, infections, and cancer. CD39-targeted approaches offer new avenues for the therapeutic modulation of the immune response in autoimmunity, infections, and cancer.
Bibliografie:ObjectType-Article-1
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ISSN:1471-4906
1471-4981
1471-4981
DOI:10.1016/j.it.2016.04.009