Myeloid-Derived Suppressor Cells in Lung Transplantation
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after...
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Frontiers Media S.A.
2019-04-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00900/full |
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doaj-938adce2f6dd4fdc9773cfd298f69029 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tobias Heigl Anurag Singh Berta Saez-Gimenez Janne Kaes Anke Van Herck Annelore Sacreas Hanne Beeckmans Arno Vanstapel Stijn E. Verleden Dirk E. Van Raemdonck Geert Verleden Bart M. Vanaudenaerde Dominik Hartl Robin Vos |
spellingShingle |
Tobias Heigl Anurag Singh Berta Saez-Gimenez Janne Kaes Anke Van Herck Annelore Sacreas Hanne Beeckmans Arno Vanstapel Stijn E. Verleden Dirk E. Van Raemdonck Geert Verleden Bart M. Vanaudenaerde Dominik Hartl Robin Vos Myeloid-Derived Suppressor Cells in Lung Transplantation Frontiers in Immunology myeloid-derived suppressor cells blood lung transplantation allograft chronic rejection immunosuppression |
author_facet |
Tobias Heigl Anurag Singh Berta Saez-Gimenez Janne Kaes Anke Van Herck Annelore Sacreas Hanne Beeckmans Arno Vanstapel Stijn E. Verleden Dirk E. Van Raemdonck Geert Verleden Bart M. Vanaudenaerde Dominik Hartl Robin Vos |
author_sort |
Tobias Heigl |
title |
Myeloid-Derived Suppressor Cells in Lung Transplantation |
title_short |
Myeloid-Derived Suppressor Cells in Lung Transplantation |
title_full |
Myeloid-Derived Suppressor Cells in Lung Transplantation |
title_fullStr |
Myeloid-Derived Suppressor Cells in Lung Transplantation |
title_full_unstemmed |
Myeloid-Derived Suppressor Cells in Lung Transplantation |
title_sort |
myeloid-derived suppressor cells in lung transplantation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-04-01 |
description |
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression. Granulocytic (G)-MDSC were identified and quantified by flow cytometry of blood from 4 control subjects and 20 lung transplant patients (stable n = 6, infection n = 5; CLAD n = 9). G-MDSC functionality was assessed in vitro by their capability to block CD4 and CD8 T cell proliferation. More G-MDSC could be assessed using EDTA tubes compared to heparin tubes (p = 0.004). G-MDSC were increased in stable lung transplant recipients vs. non-transplant controls (52.1% vs. 9.4%; p = 0.0095). The infection or CLAD groups had lower G-MDSCs vs. stable recipients (28.2%p = 0.041 and 33.0%; p = 0.088, respectively), but were not different among CLAD phenotypes. G-MDSC tended to correlate with cyclosporine A and tacrolimus levels (r2 = 0.18; r2 = 0.17). CD4 and CD8 cells proliferation decreased by 50 and 80% if co-cultured with MDSCs (1:6 and 1:2 MDSC:T-cell ratio, respectively). In conclusion, circulating MDSCs are measurable, functional and have a G-MDSC phenotype in lung transplant patients. Their frequency is increased in stable patients, decreased during post-transplant complications, and related to level of immunosuppression. This study may pave the way for further investigations of MDSC in the context of lung transplantation. |
topic |
myeloid-derived suppressor cells blood lung transplantation allograft chronic rejection immunosuppression |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00900/full |
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doaj-938adce2f6dd4fdc9773cfd298f690292020-11-25T01:55:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00900444808Myeloid-Derived Suppressor Cells in Lung TransplantationTobias Heigl0Anurag Singh1Berta Saez-Gimenez2Janne Kaes3Anke Van Herck4Annelore Sacreas5Hanne Beeckmans6Arno Vanstapel7Stijn E. Verleden8Dirk E. Van Raemdonck9Geert Verleden10Bart M. Vanaudenaerde11Dominik Hartl12Robin Vos13Lung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumUniversitätsklinik für Kinder-und Jugendmedizin, Tübingen, GermanyLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumUniversitätsklinik für Kinder-und Jugendmedizin, Tübingen, GermanyLung Transplant Unit, Lab of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, BelgiumMyeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression. Granulocytic (G)-MDSC were identified and quantified by flow cytometry of blood from 4 control subjects and 20 lung transplant patients (stable n = 6, infection n = 5; CLAD n = 9). G-MDSC functionality was assessed in vitro by their capability to block CD4 and CD8 T cell proliferation. More G-MDSC could be assessed using EDTA tubes compared to heparin tubes (p = 0.004). G-MDSC were increased in stable lung transplant recipients vs. non-transplant controls (52.1% vs. 9.4%; p = 0.0095). The infection or CLAD groups had lower G-MDSCs vs. stable recipients (28.2%p = 0.041 and 33.0%; p = 0.088, respectively), but were not different among CLAD phenotypes. G-MDSC tended to correlate with cyclosporine A and tacrolimus levels (r2 = 0.18; r2 = 0.17). CD4 and CD8 cells proliferation decreased by 50 and 80% if co-cultured with MDSCs (1:6 and 1:2 MDSC:T-cell ratio, respectively). In conclusion, circulating MDSCs are measurable, functional and have a G-MDSC phenotype in lung transplant patients. Their frequency is increased in stable patients, decreased during post-transplant complications, and related to level of immunosuppression. This study may pave the way for further investigations of MDSC in the context of lung transplantation.https://www.frontiersin.org/article/10.3389/fimmu.2019.00900/fullmyeloid-derived suppressor cellsbloodlung transplantationallograftchronic rejectionimmunosuppression |