title: CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression.
abstract: Extracellular ATP is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. However, extracellular adenosine acts as an immunoregulatory signal that modulates the function of several cellular components of the adaptive and innate immune response. Consequently, the balance between ATP and adenosine concentration is crucial in immune homeostasis. CD39 and CD73 are two ectonucleotidases that cooperate in the generation of extracellular adenosine through ATP hydrolysis, thus tilting the balance towards immunosuppressive microenvironments. Extracellular adenosine can prevent activation, proliferation, cytokine production and cytotoxicity in T cells through the stimulation of the A2A receptor; however, recent evidence has shown that adenosine may also affect other processes in T-cell biology. In this review, we discuss evidence that supports a role of CD73 and CD39 ectonucleotidases in controlling naive T-cell homeostasis and memory cell survival through adenosine production. Finally, we propose a novel hypothesis of a possible role of these ectonucleotidases and autocrine adenosine signaling in controlling T-cell differentiation.
authors.affiliation: Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Bono
authors.affiliation: Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
authors.forename: Dominique
authors.initials: D
authors.lastname: Fernández
authors.affiliation: Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Flores-Santibáñez
authors.affiliation: Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile; Fundacion Ciencia y Vida, Santiago, Chile; Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosemblatt
authors.affiliation: Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. Electronic address: dsauma@u.uchile.cl.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sauma
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D007108:Immune Tolerance; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine
keywords: Adenosine; CD39; CD73; Differentiation; Ectonucleotidase; T cell