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Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection

Organ transplantation is the optimal treatment for patients with end‐stage diseases. T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal ther...

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Autores principales: Luo, Zihuan, Liao, Tao, Zhang, Yannan, Zheng, Haofeng, Sun, Qipeng, Han, Fei, Ma, Maolin, Ye, Yongrong, Sun, Qiquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472007/
https://www.ncbi.nlm.nih.gov/pubmed/36176616
http://dx.doi.org/10.1002/btm2.10316
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author Luo, Zihuan
Liao, Tao
Zhang, Yannan
Zheng, Haofeng
Sun, Qipeng
Han, Fei
Ma, Maolin
Ye, Yongrong
Sun, Qiquan
author_facet Luo, Zihuan
Liao, Tao
Zhang, Yannan
Zheng, Haofeng
Sun, Qipeng
Han, Fei
Ma, Maolin
Ye, Yongrong
Sun, Qiquan
author_sort Luo, Zihuan
collection PubMed
description Organ transplantation is the optimal treatment for patients with end‐stage diseases. T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft. Here, we developed a membrane‐anchored‐protein PD‐L1 (map‐PD‐L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD‐L1 increased directly with map‐PD‐L1 concentration and incubation time. Moreover, map‐PD‐L1 was even stably anchored to rgEC at low temperature. Map‐PD‐L1 could bind to PD‐1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map‐PD‐L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map‐PD‐L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long‐term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map‐PD‐L1 might provide a viable clinical option for organ‐targeted induction therapy in organ transplantation.
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spelling pubmed-94720072022-09-28 Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection Luo, Zihuan Liao, Tao Zhang, Yannan Zheng, Haofeng Sun, Qipeng Han, Fei Ma, Maolin Ye, Yongrong Sun, Qiquan Bioeng Transl Med Research Articles Organ transplantation is the optimal treatment for patients with end‐stage diseases. T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft. Here, we developed a membrane‐anchored‐protein PD‐L1 (map‐PD‐L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD‐L1 increased directly with map‐PD‐L1 concentration and incubation time. Moreover, map‐PD‐L1 was even stably anchored to rgEC at low temperature. Map‐PD‐L1 could bind to PD‐1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map‐PD‐L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map‐PD‐L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long‐term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map‐PD‐L1 might provide a viable clinical option for organ‐targeted induction therapy in organ transplantation. John Wiley & Sons, Inc. 2022-04-06 /pmc/articles/PMC9472007/ /pubmed/36176616 http://dx.doi.org/10.1002/btm2.10316 Text en © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Luo, Zihuan
Liao, Tao
Zhang, Yannan
Zheng, Haofeng
Sun, Qipeng
Han, Fei
Ma, Maolin
Ye, Yongrong
Sun, Qiquan
Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title_full Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title_fullStr Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title_full_unstemmed Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title_short Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection
title_sort ex vivo anchored pd‐l1 functionally prevent in vivo renal allograft rejection
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472007/
https://www.ncbi.nlm.nih.gov/pubmed/36176616
http://dx.doi.org/10.1002/btm2.10316
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