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Updated: Mar 23, 2026
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Unlocking the Potential of Purinergic Signaling in Transplantation
R Zeiser1, S C Robson2, T Vaikunthanathan3
1Department of Hematology and Oncology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany.
Abstract:
Purinergic signaling has been recognized as playing an important role in inflammation, angiogenesis, malignancy, diabetes and neural transmission. Activation of signaling pathways downstream from purinergic receptors may also be implicated in transplantation and related vascular injury. Following transplantation, the proinflammatory "danger signal" adenosine triphosphate (ATP) is released from damaged cells and promotes proliferation and activation of a variety of immune cells. Targeting purinergic signaling pathways may promote immunosuppression and ameliorate inflammation. Under pathophysiological conditions, nucleotide-scavenging ectonucleotidases CD39 and CD73 hydrolyze ATP, ultimately, to the anti-inflammatory mediator adenosine. Adenosine suppresses proinflammatory cytokine production and is associated with improved graft survival and decreased severity of graft-versus-host disease. Furthermore, purinergic signaling is involved both directly and indirectly in the mechanism of action of several existing immunosuppressive drugs, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. Targeting of purinergic receptor pathways, particularly in the setting of combination therapies, could become a valuable immunosuppressive strategy in transplantation. This review focuses on the role of the purinergic signaling pathway in transplantation and immunosuppression and explores possible future applications in clinical practice.
Insights
Targeting purinergic signaling pathways, which involve adenosine triphosphate (ATP) and adenosine, can promote immunosuppression and reduce inflammation in transplantation. This strategy may improve graft survival and decrease graft-versus-host disease severity.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Biology
Background:
- Purinergic signaling regulates key processes including inflammation, angiogenesis, and neural transmission.
- Dysregulated purinergic signaling contributes to vascular injury and immune responses post-transplantation.
- Adenosine triphosphate (ATP) acts as a danger signal, activating immune cells and promoting inflammation.
Purpose of the Study:
- To review the role of purinergic signaling in transplantation and immunosuppression.
- To explore the therapeutic potential of targeting purinergic pathways in clinical practice.
- To highlight the connection between purinergic signaling and existing immunosuppressive drugs.
Main Methods:
- Literature review of purinergic signaling in transplantation.
- Analysis of ectonucleotidases (CD39 and CD73) in modulating immune responses.
- Examination of purinergic receptor involvement in immunosuppressive drug mechanisms.
Main Results:
- Ectonucleotidases CD39 and CD73 convert ATP to anti-inflammatory adenosine.
- Adenosine suppresses proinflammatory cytokines, enhancing graft survival and reducing graft-versus-host disease.
- Purinergic signaling is integral to the action of calcineurin and mTOR inhibitors.
Conclusions:
- Targeting purinergic signaling pathways offers a promising strategy for immunosuppression in transplantation.
- Combination therapies involving purinergic receptor modulation may improve outcomes.
- Further clinical applications of purinergic signaling modulation in transplantation are anticipated.
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