Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation

Abstract Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T...

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Autores principales: Maryam Tahvildari, Parisa Emami-Naeini, Masahiro Omoto, Alireza Mashaghi, Sunil K. Chauhan, Reza Dana
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/9304f3c665fa45cbb38460c64f6e63d2
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spelling oai:doaj.org-article:9304f3c665fa45cbb38460c64f6e63d22021-12-02T12:32:04ZTreatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation10.1038/s41598-017-01065-z2045-2322https://doaj.org/article/9304f3c665fa45cbb38460c64f6e63d22017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01065-zhttps://doaj.org/toc/2045-2322Abstract Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-β1 (TGFβ1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)+ effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+ cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.Maryam TahvildariParisa Emami-NaeiniMasahiro OmotoAlireza MashaghiSunil K. ChauhanReza DanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maryam Tahvildari
Parisa Emami-Naeini
Masahiro Omoto
Alireza Mashaghi
Sunil K. Chauhan
Reza Dana
Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
description Abstract Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-β1 (TGFβ1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)+ effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+ cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.
format article
author Maryam Tahvildari
Parisa Emami-Naeini
Masahiro Omoto
Alireza Mashaghi
Sunil K. Chauhan
Reza Dana
author_facet Maryam Tahvildari
Parisa Emami-Naeini
Masahiro Omoto
Alireza Mashaghi
Sunil K. Chauhan
Reza Dana
author_sort Maryam Tahvildari
title Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
title_short Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
title_full Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
title_fullStr Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
title_full_unstemmed Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
title_sort treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9304f3c665fa45cbb38460c64f6e63d2
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