CD4 + FoxP3 + CD73 + regulatory T cell promotes cardiac healing post-myocardial infarction
Despite recent studies indicating a crucial role of ecto-5'-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73 regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear. We sought to investigate the contributio...
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Veröffentlicht in: | Theranostics 2022-01, Vol.12 (6), p.2707-2721 |
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Zusammenfassung: | Despite recent studies indicating a crucial role of ecto-5'-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73
regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear. We sought to investigate the contribution of CD73 on Tregs to the resolution of cardiac inflammation and remodeling after MI.
Cardiac function, tissue injury, Tregs percentage in injured hearts, and purinergic signaling changes in cardiac FoxP3
Tregs were analyzed after permanent descending coronary artery ligation. CD73 knockout Tregs were used to determine the function of CD73 on Tregs. Peripheral blood mononuclear cells (PBMCs) from acute myocardial infarction (AMI) patients and matched non-MI subjects were assessed via flow cytometry.
Cardiac Tregs exhibited distinction of purinergic signaling post MI with dramatically high level of CD73 compared to the sham Tregs. CD73 deficiency decreased the tissue tropism, and impaired the immunosuppressive and protective function of Tregs in cardiac healing. Administration of low-dose of IL-2/anti-IL-2 complex resulted in FoxP3
CD73
Tregs expansion in the heart and contributed to the recovery of cardiac function. CD73 derived from FoxP3
Tregs could bind to FoxP3
effector T-cells and inhibit the production of multiple inflammatory cytokines. In AMI patients, CD73 expressions on both CD4
cells and FoxP3
Tregs decreased in PBMCs. Moreover, CD73 expressions on CD4
T cells were negatively correlated with the levels of NT pro-BNP and myocardial zymogram in serum.
Our findings indicated the importance of FoxP3
CD73
Tregs in inflammation resolution and cardiac healing post-MI. |
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ISSN: | 1838-7640 1838-7640 |
DOI: | 10.7150/thno.68437 |