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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Autores principales: William Foulsham, Sharad K. Mittal, Takeshi Nakao, Giulia Coco, Yukako Taketani, Sunil K. Chauhan, Reza Dana
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Publicado: Nature Portfolio 2019
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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