The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection
Abstract Adenosine triphosphate (ATP) is released into the extracellular environment during transplantation, and acts via purinergic receptors to amplify the alloimmune response. Here, using a well-established murine model of allogeneic corneal transplantation, we investigated the immunomodulatory m...
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2019
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oai:doaj.org-article:ab2e2f2678754b1596ab77c1e6dae7fd2021-12-02T15:10:01ZThe purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection10.1038/s41598-019-44973-y2045-2322https://doaj.org/article/ab2e2f2678754b1596ab77c1e6dae7fd2019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44973-yhttps://doaj.org/toc/2045-2322Abstract Adenosine triphosphate (ATP) is released into the extracellular environment during transplantation, and acts via purinergic receptors to amplify the alloimmune response. Here, using a well-established murine model of allogeneic corneal transplantation, we investigated the immunomodulatory mechanisms of the purinergic receptor antagonist oxidized ATP (oATP). Corneal transplantation was performed using C57BL/6 donors and BALB/c hosts. oATP or sterile saline was administered via intraperitoneal injection for 2 weeks postoperatively. Frequencies of CD45+ leukocytes, CD11b+MHCII+ antigen presenting cells (APCs), CD4+IFN-γ+ effector Th1 cells and CD4+Foxp3+ regulatory T cells (Tregs) were evaluated by flow cytometry. Slit-lamp microscopy was performed weekly for 8 weeks to evaluate graft opacity and determine transplant rejection. Treatment with oATP was shown to significantly reduce graft infiltration of CD45+ leukocytes, decrease APC maturation and suppress effector Th1 cell generation relative to saline-treated control. No difference in Treg frequencies or Foxp3 expression was observed between the oATP-treated and control groups. Finally, oATP treatment was shown to reduce graft opacity and increase graft survival. This report demonstrates that oATP limits the alloimmune response by regulating APC maturation and suppressing the generation of alloreactive Th1 immunity.William FoulshamSharad K. MittalTakeshi NakaoGiulia CocoYukako TaketaniSunil K. ChauhanReza DanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-8 (2019) |
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Medicine R Science Q William Foulsham Sharad K. Mittal Takeshi Nakao Giulia Coco Yukako Taketani Sunil K. Chauhan Reza Dana The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
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Abstract Adenosine triphosphate (ATP) is released into the extracellular environment during transplantation, and acts via purinergic receptors to amplify the alloimmune response. Here, using a well-established murine model of allogeneic corneal transplantation, we investigated the immunomodulatory mechanisms of the purinergic receptor antagonist oxidized ATP (oATP). Corneal transplantation was performed using C57BL/6 donors and BALB/c hosts. oATP or sterile saline was administered via intraperitoneal injection for 2 weeks postoperatively. Frequencies of CD45+ leukocytes, CD11b+MHCII+ antigen presenting cells (APCs), CD4+IFN-γ+ effector Th1 cells and CD4+Foxp3+ regulatory T cells (Tregs) were evaluated by flow cytometry. Slit-lamp microscopy was performed weekly for 8 weeks to evaluate graft opacity and determine transplant rejection. Treatment with oATP was shown to significantly reduce graft infiltration of CD45+ leukocytes, decrease APC maturation and suppress effector Th1 cell generation relative to saline-treated control. No difference in Treg frequencies or Foxp3 expression was observed between the oATP-treated and control groups. Finally, oATP treatment was shown to reduce graft opacity and increase graft survival. This report demonstrates that oATP limits the alloimmune response by regulating APC maturation and suppressing the generation of alloreactive Th1 immunity. |
format |
article |
author |
William Foulsham Sharad K. Mittal Takeshi Nakao Giulia Coco Yukako Taketani Sunil K. Chauhan Reza Dana |
author_facet |
William Foulsham Sharad K. Mittal Takeshi Nakao Giulia Coco Yukako Taketani Sunil K. Chauhan Reza Dana |
author_sort |
William Foulsham |
title |
The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
title_short |
The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
title_full |
The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
title_fullStr |
The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
title_full_unstemmed |
The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
title_sort |
purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection |
publisher |
Nature Portfolio |
publishDate |
2019 |
url |
https://doaj.org/article/ab2e2f2678754b1596ab77c1e6dae7fd |
work_keys_str_mv |
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