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Targeting Adenosine Receptor Signaling in Cancer Immunotherapy
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Dysregulation of Adenosinergic Signaling in Systemic and Organ-Specific Autoimmunity

1
Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
2
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 528; https://doi.org/10.3390/ijms20030528
Received: 19 December 2018 / Revised: 18 January 2019 / Accepted: 22 January 2019 / Published: 27 January 2019
(This article belongs to the Special Issue Purinergic Signalling in Cancer and Inflammation)
Exact causes for autoimmune diseases remain unclear and no cures are available. Breakdown of immunotolerance could set the stage for unfettered immune responses that target self-antigens. Impaired regulatory immune mechanisms could have permissive roles in autoreactivity. Abnormal regulatory immune cell function, therefore, might be a major determinant of the pathogenesis of autoimmune disease. All current treatments are associated with some level of clinical toxicity. Treatment to specifically target dysregulated immunity in these diseases would be a great advance. Extracellular adenosine is a signaling mediator that suppresses inflammation through activation of P1 receptors, most active under pathological conditions. Mounting evidence has linked alterations in the generation of adenosine from extracellular nucleotides by ectonucleotidases, and associated perturbations in purinergic signaling, to the immunological disruption and loss of immunotolerance in autoimmunity. Targeted modulation of the purinergic signaling by either targeting ectonucleotidases or modulating P1 purinergic receptors could therefore restore the balance between autoreactive immune responses; and thereby allow reestablishment of immunotolerance. We review the roles of CD39 and CD73 ectoenzymes in inflammatory states and with the dysregulation of P1 receptor signaling in systemic and organ-specific autoimmunity. Correction of such perturbations could be exploited in potential therapeutic applications. View Full-Text
Keywords: ectonucleotidase; adenosine; adenosine receptor; autoimmunity; T-cell ectonucleotidase; adenosine; adenosine receptor; autoimmunity; T-cell
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Vuerich, M.; Harshe, R.P.; Robson, S.C.; Longhi, M.S. Dysregulation of Adenosinergic Signaling in Systemic and Organ-Specific Autoimmunity. Int. J. Mol. Sci. 2019, 20, 528.

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