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Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells

OBJECTIVE: To explore the roles of human mesenchymal stem cell (hMSC) death-associated protein kinase 1 (DAPK1) in modulating CD4+ T lymphocyte proliferation. METHODS: Human MSCs and peripheral blood mononuclear cells were isolated and cocultured in vitro for 3 days. Lentiviral-mediated RNA interfer...

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Autores principales: Wang, Shan, Su, Hongjun, Feng, Pei, Deng, Wen, Su, Chunyan, Wu, Yanfeng, Shen, Huiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323303/
https://www.ncbi.nlm.nih.gov/pubmed/32586165
http://dx.doi.org/10.1177/0300060520933453
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author Wang, Shan
Su, Hongjun
Feng, Pei
Deng, Wen
Su, Chunyan
Wu, Yanfeng
Shen, Huiyong
author_facet Wang, Shan
Su, Hongjun
Feng, Pei
Deng, Wen
Su, Chunyan
Wu, Yanfeng
Shen, Huiyong
author_sort Wang, Shan
collection PubMed
description OBJECTIVE: To explore the roles of human mesenchymal stem cell (hMSC) death-associated protein kinase 1 (DAPK1) in modulating CD4+ T lymphocyte proliferation. METHODS: Human MSCs and peripheral blood mononuclear cells were isolated and cocultured in vitro for 3 days. Lentiviral-mediated RNA interference (LV-sh-DAPK1) was used to silence DAPK1 expression in hMSCs. Expression of DAPK1 was assessed by western blotting. Transcriptional levels of DAPK1, transforming growth factor-β1, indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, interleukin (IL)-6, suppressor of cytokine signaling 1, IL-10 and cyclooxygenase-2 were investigated by quantitative PCR. Levels of IL-10 were assessed by ELISA. Proliferation of CD4+ T cells was assessed by flow cytometry. RESULTS: DAPK1 was abundantly expressed in ex vivo-expanded hMSCs and expression was positively correlated with hMSC suppression of CD4+ T cell proliferation. Silencing of DAPK1 in hMSCs reduced the ability of these cells to inhibit CD4+ T cell proliferation and resulted in decreased IL-10 levels compared with untreated controls. Exogenous supplementation with recombinant human IL-10 in DAPK1-silenced hMSCs restored immunosuppression of CD4+ T cells. CONCLUSIONS: The DAPK1-IL-10 axis mediates a novel immunoregulatory function of hMSCs toward CD4+ T cells.
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spelling pubmed-73233032020-07-06 Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells Wang, Shan Su, Hongjun Feng, Pei Deng, Wen Su, Chunyan Wu, Yanfeng Shen, Huiyong J Int Med Res Pre-Clinical Research Report OBJECTIVE: To explore the roles of human mesenchymal stem cell (hMSC) death-associated protein kinase 1 (DAPK1) in modulating CD4+ T lymphocyte proliferation. METHODS: Human MSCs and peripheral blood mononuclear cells were isolated and cocultured in vitro for 3 days. Lentiviral-mediated RNA interference (LV-sh-DAPK1) was used to silence DAPK1 expression in hMSCs. Expression of DAPK1 was assessed by western blotting. Transcriptional levels of DAPK1, transforming growth factor-β1, indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, interleukin (IL)-6, suppressor of cytokine signaling 1, IL-10 and cyclooxygenase-2 were investigated by quantitative PCR. Levels of IL-10 were assessed by ELISA. Proliferation of CD4+ T cells was assessed by flow cytometry. RESULTS: DAPK1 was abundantly expressed in ex vivo-expanded hMSCs and expression was positively correlated with hMSC suppression of CD4+ T cell proliferation. Silencing of DAPK1 in hMSCs reduced the ability of these cells to inhibit CD4+ T cell proliferation and resulted in decreased IL-10 levels compared with untreated controls. Exogenous supplementation with recombinant human IL-10 in DAPK1-silenced hMSCs restored immunosuppression of CD4+ T cells. CONCLUSIONS: The DAPK1-IL-10 axis mediates a novel immunoregulatory function of hMSCs toward CD4+ T cells. SAGE Publications 2020-06-26 /pmc/articles/PMC7323303/ /pubmed/32586165 http://dx.doi.org/10.1177/0300060520933453 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Pre-Clinical Research Report
Wang, Shan
Su, Hongjun
Feng, Pei
Deng, Wen
Su, Chunyan
Wu, Yanfeng
Shen, Huiyong
Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title_full Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title_fullStr Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title_full_unstemmed Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title_short Loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of CD4+ T cells
title_sort loss of death-associated protein kinase 1 in human bone marrow mesenchymal stem cells decreases immunosuppression of cd4+ t cells
topic Pre-Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323303/
https://www.ncbi.nlm.nih.gov/pubmed/32586165
http://dx.doi.org/10.1177/0300060520933453
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