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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ab2e2f2678754b1596ab77c1e6dae7fd
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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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The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection

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