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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| Veröffentlicht in: | PloS one 2013-04, Vol.8 (4), p.e60367-e60367 |
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| creator | Al-Chaqmaqchi, Heevy Sadeghi, Behnam Abedi-Valugerdi, Manuchehr Al-Hashmi, Sulaiman Fares, Mona Kuiper, Raoul Lundahl, Joachim Hassan, Moustapha Moshfegh, Ali |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0060367 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0060367</identifier><identifier>PMID: 23593203</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal tissues ; Animals ; Antigens ; Apoptosis ; B7-H1 Antigen - genetics ; B7-H1 Antigen - immunology ; B7-H1 Antigen - metabolism ; Biology ; Bone cancer ; Bone marrow ; Bone marrow transplantation ; Bone Marrow Transplantation - immunology ; Busulfan ; Cancer ; Cell death ; Chemotherapy ; Complications ; Complications and side effects ; Conditioning ; Correlation analysis ; Cyclophosphamide ; Cytokines ; Development and progression ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic aspects ; Graft rejection ; Graft versus host disease ; Graft versus host reaction ; Graft vs Host Disease - genetics ; Graft vs Host Disease - immunology ; Graft vs Host Disease - metabolism ; Grafting ; Heart ; Hematopoietic stem cells ; Immunohistochemistry ; Immunomodulation ; Interferon-gamma - biosynthesis ; Kidney - metabolism ; Kidneys ; Laboratories ; Ligands ; Liver ; Liver - metabolism ; Liver transplants ; Lymphocytes ; Male ; Medical research ; Medicine ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Muscles ; Muscles - metabolism ; Organs ; PD-L1 protein ; Physiological aspects ; RNA, Messenger - genetics ; Serum levels ; Skeletal muscle ; Spleen ; Stem cell transplantation ; Stem cells ; Syngeneic grafts ; Transplantation ; Transplantation Conditioning ; Transplantation, Homologous ; Transplantation, Isogeneic ; Transplants & implants ; Trends ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; γ-Interferon</subject><ispartof>PloS one, 2013-04, Vol.8 (4), p.e60367-e60367</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Al-Chaqmaqchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Animal tissues</subject><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - immunology</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biology</subject><subject>Bone cancer</subject><subject>Bone marrow</subject><subject>Bone marrow transplantation</subject><subject>Bone Marrow Transplantation - immunology</subject><subject>Busulfan</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Conditioning</subject><subject>Correlation analysis</subject><subject>Cyclophosphamide</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genetic aspects</subject><subject>Graft rejection</subject><subject>Graft versus host disease</subject><subject>Graft versus host reaction</subject><subject>Graft vs Host Disease - genetics</subject><subject>Graft vs Host Disease - immunology</subject><subject>Graft vs Host Disease - metabolism</subject><subject>Grafting</subject><subject>Heart</subject><subject>Hematopoietic stem cells</subject><subject>Immunohistochemistry</subject><subject>Immunomodulation</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Kidney - metabolism</subject><subject>Kidneys</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver transplants</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Muscles</subject><subject>Muscles - metabolism</subject><subject>Organs</subject><subject>PD-L1 protein</subject><subject>Physiological aspects</subject><subject>RNA, Messenger - genetics</subject><subject>Serum levels</subject><subject>Skeletal muscle</subject><subject>Spleen</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Syngeneic grafts</subject><subject>Transplantation</subject><subject>Transplantation Conditioning</subject><subject>Transplantation, Homologous</subject><subject>Transplantation, Isogeneic</subject><subject>Transplants & implants</subject><subject>Trends</subject><subject>Tumor Necrosis Factor-alpha - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Chaqmaqchi, Heevy</au><au>Sadeghi, Behnam</au><au>Abedi-Valugerdi, Manuchehr</au><au>Al-Hashmi, Sulaiman</au><au>Fares, Mona</au><au>Kuiper, Raoul</au><au>Lundahl, Joachim</au><au>Hassan, Moustapha</au><au>Moshfegh, Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-04-04</date><risdate>2013</risdate><volume>8</volume><issue>4</issue><spage>e60367</spage><epage>e60367</epage><pages>e60367-e60367</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23593203</pmid><doi>10.1371/journal.pone.0060367</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-04, Vol.8 (4), p.e60367-e60367 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330914091 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal tissues Animals Antigens Apoptosis B7-H1 Antigen - genetics B7-H1 Antigen - immunology B7-H1 Antigen - metabolism Biology Bone cancer Bone marrow Bone marrow transplantation Bone Marrow Transplantation - immunology Busulfan Cancer Cell death Chemotherapy Complications Complications and side effects Conditioning Correlation analysis Cyclophosphamide Cytokines Development and progression Female Gene expression Gene Expression Profiling Gene Expression Regulation Genetic aspects Graft rejection Graft versus host disease Graft versus host reaction Graft vs Host Disease - genetics Graft vs Host Disease - immunology Graft vs Host Disease - metabolism Grafting Heart Hematopoietic stem cells Immunohistochemistry Immunomodulation Interferon-gamma - biosynthesis Kidney - metabolism Kidneys Laboratories Ligands Liver Liver - metabolism Liver transplants Lymphocytes Male Medical research Medicine Mice Mice, Inbred BALB C Mice, Inbred C57BL Muscles Muscles - metabolism Organs PD-L1 protein Physiological aspects RNA, Messenger - genetics Serum levels Skeletal muscle Spleen Stem cell transplantation Stem cells Syngeneic grafts Transplantation Transplantation Conditioning Transplantation, Homologous Transplantation, Isogeneic Transplants & implants Trends Tumor Necrosis Factor-alpha - biosynthesis Tumor necrosis factor-TNF Tumor necrosis factor-α γ-Interferon |
| title | The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease |
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