The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease.
Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoieti...
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doaj-6373bcb1728b493fac9db292e803b2472020-11-24T21:41:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6036710.1371/journal.pone.0060367The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease.Heevy Al-ChaqmaqchiBehnam SadeghiManuchehr Abedi-ValugerdiSulaiman Al-HashmiMona FaresRaoul KuiperJoachim LundahlMoustapha HassanAli MoshfeghProgrammed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.http://europepmc.org/articles/PMC3617218?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heevy Al-Chaqmaqchi Behnam Sadeghi Manuchehr Abedi-Valugerdi Sulaiman Al-Hashmi Mona Fares Raoul Kuiper Joachim Lundahl Moustapha Hassan Ali Moshfegh |
spellingShingle |
Heevy Al-Chaqmaqchi Behnam Sadeghi Manuchehr Abedi-Valugerdi Sulaiman Al-Hashmi Mona Fares Raoul Kuiper Joachim Lundahl Moustapha Hassan Ali Moshfegh The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. PLoS ONE |
author_facet |
Heevy Al-Chaqmaqchi Behnam Sadeghi Manuchehr Abedi-Valugerdi Sulaiman Al-Hashmi Mona Fares Raoul Kuiper Joachim Lundahl Moustapha Hassan Ali Moshfegh |
author_sort |
Heevy Al-Chaqmaqchi |
title |
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. |
title_short |
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. |
title_full |
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. |
title_fullStr |
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. |
title_full_unstemmed |
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. |
title_sort |
role of programmed cell death ligand-1 (pd-l1/cd274) in the development of graft versus host disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. |
url |
http://europepmc.org/articles/PMC3617218?pdf=render |
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