Article ; Online: Dysregulation of Adenosinergic Signaling in Systemic and Organ-Specific Autoimmunity.
International journal of molecular sciences
2019 Volume 20, Issue 3
Abstract: 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 ... ...
| Abstract | 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. |
|---|---|
| MeSH term(s) | Adenosine/metabolism ; Antigens, Neoplasm/metabolism ; Apyrase/metabolism ; Autoimmune Diseases/drug therapy ; Autoimmune Diseases/metabolism ; Humans ; Organ Specificity ; Receptors, Purinergic P1/metabolism ; Signal Transduction ; Tetraspanins/metabolism |
| Chemical Substances | Antigens, Neoplasm ; CD37 protein, human ; Receptors, Purinergic P1 ; Tetraspanins ; Apyrase (EC 3.6.1.5) ; ENTPD1 protein, human (EC 3.6.1.5) ; Adenosine (K72T3FS567) |
| Language | English |
| Publishing date | 2019-01-27 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Review |
| ZDB-ID | 2019364-6 |
| ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
| ISSN (online) | 1422-0067 |
| ISSN | 1422-0067 ; 1661-6596 |
| DOI | 10.3390/ijms20030528 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.