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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Nature Portfolio
2017
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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) |
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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 |
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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 |
work_keys_str_mv |
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