Adenosine triphosphate (ATP) is a pro-inflammatory mediator that regulates cell metabolism, migration, proliferation and apoptosis upon binding to P2X and P2Y receptors. In the extracellular environment, ATP is rapidly hydrolyzed to generate adenosine monophosphate (AMP) and ultimately adenosine, which signals through the P1 receptors and mediates immunosuppression. There are four adenosine receptors, namely: A1, A2A, A2B and A3. Upon binding to adenosine, these receptors can either inhibit adenylate cyclase and cyclic AMP (cAMP) production (A1 and A3 receptors) or favor cAMP accumulation (A2A and A2B receptors). This, in turn, activates the protein kinase A and the EPAC signaling pathways. The generation of AMP and adenosine from ATP is orchestrated by families of enzymes known as ectonucleotidases. These include (i) ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1 or CD39), the prototype of this class of enzymes; (ii) ecto-nucleotide pyrophosphate phosphodiesterases (E-NPP); (iii) the NAD glycohydrolyses; (iv) CD38/NADase; alkaline phosphatases; (v) adenylate kinase; (vi) the nucleoside diphosphate kinase; and (vii) the ecto-F1-F0 ATP synthases.
ENTPDase enzymes – the focus of this Research Topic – differ with regard to their hydrolytic activities. NTPDase I catalyzes both ATP and ADP; NTPDase 3 and 8 preferentially hydrolyze ATP while NTPDase 2 hydrolyzes ATP only. The AMP derived from this catalytic activity is then converted into adenosine by the ecto-5’-nucleotidase CD73.
Ectonucleotidases are expressed on a variety of immune and non-immune cells and due to their scavenging properties, they ultimately lead to the generation of immunoregulatory mediators which govern inflammation throughout both acute and chronic phases. In the immune system, ectonucleotidases are expressed by a variety of adaptive and innate immune cell types including B cells; myeloid cells , various T cell subsets and NK cells. In monocytes, the absence of CD39 has been associated with the inability to transition to a regulatory state. In dendritic cells, a lack of CD39 has been linked to defective antigen presentation and response to haptens. In regulatory T cell subsets, ectonucleotidases have been demonstrated to be involved in regulating mechanisms of immunosuppression via the generation of adenosine. In addition, in Th17 cells, CD39 expression has been demonstrated to limit the pathogenic potential of this cell type.
This Research Topic aims to provide an extensive overview on the role of ectonucleotidases, chiefly ENTPD1/CD39 and CD73, in the modulation in immune cells during acute and chronic inflammatory phases in the following conditions: pathologies of the lung and kidney; intestinal and hepatic inflammatory disorders; hematological disorders and malignancies and in solid tumors.
We welcome the submission of Reviews and Mini-Reviews that aim to discuss the following sub-topics:
(i) How and to what extent ectonucleotidases regulate immune cells in inflammatory conditions and impact on signalling pathways in immune cells involved in inflammation.
(ii) How the dysregulation or dysfunction of ectonucleotidases in immune cells can impact on disease outcome.
(iii) How the correction/manipulation of the signaling pathways orchestrated by ectonucleotidases in immune cells could be exploited for future therapeutic interventions to halt tissue injury and prevent progression of organ damage.
Adenosine triphosphate (ATP) is a pro-inflammatory mediator that regulates cell metabolism, migration, proliferation and apoptosis upon binding to P2X and P2Y receptors. In the extracellular environment, ATP is rapidly hydrolyzed to generate adenosine monophosphate (AMP) and ultimately adenosine, which signals through the P1 receptors and mediates immunosuppression. There are four adenosine receptors, namely: A1, A2A, A2B and A3. Upon binding to adenosine, these receptors can either inhibit adenylate cyclase and cyclic AMP (cAMP) production (A1 and A3 receptors) or favor cAMP accumulation (A2A and A2B receptors). This, in turn, activates the protein kinase A and the EPAC signaling pathways. The generation of AMP and adenosine from ATP is orchestrated by families of enzymes known as ectonucleotidases. These include (i) ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1 or CD39), the prototype of this class of enzymes; (ii) ecto-nucleotide pyrophosphate phosphodiesterases (E-NPP); (iii) the NAD glycohydrolyses; (iv) CD38/NADase; alkaline phosphatases; (v) adenylate kinase; (vi) the nucleoside diphosphate kinase; and (vii) the ecto-F1-F0 ATP synthases.
ENTPDase enzymes – the focus of this Research Topic – differ with regard to their hydrolytic activities. NTPDase I catalyzes both ATP and ADP; NTPDase 3 and 8 preferentially hydrolyze ATP while NTPDase 2 hydrolyzes ATP only. The AMP derived from this catalytic activity is then converted into adenosine by the ecto-5’-nucleotidase CD73.
Ectonucleotidases are expressed on a variety of immune and non-immune cells and due to their scavenging properties, they ultimately lead to the generation of immunoregulatory mediators which govern inflammation throughout both acute and chronic phases. In the immune system, ectonucleotidases are expressed by a variety of adaptive and innate immune cell types including B cells; myeloid cells , various T cell subsets and NK cells. In monocytes, the absence of CD39 has been associated with the inability to transition to a regulatory state. In dendritic cells, a lack of CD39 has been linked to defective antigen presentation and response to haptens. In regulatory T cell subsets, ectonucleotidases have been demonstrated to be involved in regulating mechanisms of immunosuppression via the generation of adenosine. In addition, in Th17 cells, CD39 expression has been demonstrated to limit the pathogenic potential of this cell type.
This Research Topic aims to provide an extensive overview on the role of ectonucleotidases, chiefly ENTPD1/CD39 and CD73, in the modulation in immune cells during acute and chronic inflammatory phases in the following conditions: pathologies of the lung and kidney; intestinal and hepatic inflammatory disorders; hematological disorders and malignancies and in solid tumors.
We welcome the submission of Reviews and Mini-Reviews that aim to discuss the following sub-topics:
(i) How and to what extent ectonucleotidases regulate immune cells in inflammatory conditions and impact on signalling pathways in immune cells involved in inflammation.
(ii) How the dysregulation or dysfunction of ectonucleotidases in immune cells can impact on disease outcome.
(iii) How the correction/manipulation of the signaling pathways orchestrated by ectonucleotidases in immune cells could be exploited for future therapeutic interventions to halt tissue injury and prevent progression of organ damage.