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Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis
Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional kn...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377163/ https://www.ncbi.nlm.nih.gov/pubmed/34421916 http://dx.doi.org/10.3389/fimmu.2021.710904 |
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author | Xu, Heng Yu, Jizhang Cui, Jikai Chen, Zhang Zhang, Xi Zou, Yanqiang Du, Yifan Li, Yuan Le, Sheng Jiang, Lang Xia, Jiahong Wu, Jie |
author_facet | Xu, Heng Yu, Jizhang Cui, Jikai Chen, Zhang Zhang, Xi Zou, Yanqiang Du, Yifan Li, Yuan Le, Sheng Jiang, Lang Xia, Jiahong Wu, Jie |
author_sort | Xu, Heng |
collection | PubMed |
description | Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4(+) T cells in the Birc5(-/-) group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5 (-/-) mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection. |
format | Online Article Text |
id | pubmed-8377163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83771632021-08-21 Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis Xu, Heng Yu, Jizhang Cui, Jikai Chen, Zhang Zhang, Xi Zou, Yanqiang Du, Yifan Li, Yuan Le, Sheng Jiang, Lang Xia, Jiahong Wu, Jie Front Immunol Immunology Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4(+) T cells in the Birc5(-/-) group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5 (-/-) mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8377163/ /pubmed/34421916 http://dx.doi.org/10.3389/fimmu.2021.710904 Text en Copyright © 2021 Xu, Yu, Cui, Chen, Zhang, Zou, Du, Li, Le, Jiang, Xia and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Xu, Heng Yu, Jizhang Cui, Jikai Chen, Zhang Zhang, Xi Zou, Yanqiang Du, Yifan Li, Yuan Le, Sheng Jiang, Lang Xia, Jiahong Wu, Jie Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title | Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title_full | Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title_fullStr | Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title_full_unstemmed | Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title_short | Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis |
title_sort | ablation of survivin in t cells attenuates acute allograft rejection after murine heterotopic heart transplantation by inducing apoptosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377163/ https://www.ncbi.nlm.nih.gov/pubmed/34421916 http://dx.doi.org/10.3389/fimmu.2021.710904 |
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