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GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice

OBJECTIVE: This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte–macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo. METHODS: BM cell differentiation t...

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Autores principales: Zhao, Shuguang, Li, Shaohua, Yang, Jingci, Gao, Weinian, Chen, Ziying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422167/
https://www.ncbi.nlm.nih.gov/pubmed/36031660
http://dx.doi.org/10.1186/s40001-022-00788-8
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author Zhao, Shuguang
Li, Shaohua
Yang, Jingci
Gao, Weinian
Chen, Ziying
author_facet Zhao, Shuguang
Li, Shaohua
Yang, Jingci
Gao, Weinian
Chen, Ziying
author_sort Zhao, Shuguang
collection PubMed
description OBJECTIVE: This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte–macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo. METHODS: BM cell differentiation to CD11b + GR-1 + MDSCs was achieved by in vitro culture with TSA and GM-CSF, and the collected cells were analyzed by mixed lymphocyte culture to identify suppressive actions against effector T cells. RT-PCR and ELISA were conducted to analyze the CCL5 mRNA and protein levels in TSA + GM-CSF + BM, GR-1 + MDSCs and GR-1 + MDSC + CCL5 groups. The survival of cardiac grafts was compared between groups. RESULTS: TSA was beneficial for the GM-CSF-mediated BM differentiation to CD11b + GR-1 + MDSCs. Adoptive transfer of GR-1 + MDSCs was powerful in suppressing CD4 + CD25-T cell proliferation and the effect was mediated by iNOS and HO-1; it also increased CCL5 gradient concentration between grafts and plasma to recruit Treg to grafts and prolong the survival of the grafts. Survival analysis revealed that the survival of grafts after adoptive transfer of GR-1 + MDSCs could be prolonged. CONCLUSION: This study helps in further research on the application value of MDSCs in the field of transplant, and may provide a new thought for the cell therapy in inducing immune tolerance in organ transplant.
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spelling pubmed-94221672022-08-30 GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice Zhao, Shuguang Li, Shaohua Yang, Jingci Gao, Weinian Chen, Ziying Eur J Med Res Research OBJECTIVE: This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte–macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo. METHODS: BM cell differentiation to CD11b + GR-1 + MDSCs was achieved by in vitro culture with TSA and GM-CSF, and the collected cells were analyzed by mixed lymphocyte culture to identify suppressive actions against effector T cells. RT-PCR and ELISA were conducted to analyze the CCL5 mRNA and protein levels in TSA + GM-CSF + BM, GR-1 + MDSCs and GR-1 + MDSC + CCL5 groups. The survival of cardiac grafts was compared between groups. RESULTS: TSA was beneficial for the GM-CSF-mediated BM differentiation to CD11b + GR-1 + MDSCs. Adoptive transfer of GR-1 + MDSCs was powerful in suppressing CD4 + CD25-T cell proliferation and the effect was mediated by iNOS and HO-1; it also increased CCL5 gradient concentration between grafts and plasma to recruit Treg to grafts and prolong the survival of the grafts. Survival analysis revealed that the survival of grafts after adoptive transfer of GR-1 + MDSCs could be prolonged. CONCLUSION: This study helps in further research on the application value of MDSCs in the field of transplant, and may provide a new thought for the cell therapy in inducing immune tolerance in organ transplant. BioMed Central 2022-08-29 /pmc/articles/PMC9422167/ /pubmed/36031660 http://dx.doi.org/10.1186/s40001-022-00788-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhao, Shuguang
Li, Shaohua
Yang, Jingci
Gao, Weinian
Chen, Ziying
GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title_full GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title_fullStr GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title_full_unstemmed GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title_short GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
title_sort gm-csf-mediated inducement of bone marrow mdscs by tsa and effect on survival of graft in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422167/
https://www.ncbi.nlm.nih.gov/pubmed/36031660
http://dx.doi.org/10.1186/s40001-022-00788-8
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