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A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed l...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Stem Cell Research
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657938/ https://www.ncbi.nlm.nih.gov/pubmed/31242717 http://dx.doi.org/10.15283/ijsc18098 |
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author | Yi, Tac-Ghee Cho, Yun-Kyoung Lee, Hyun-Joo Kim, Junghee Jeon, Myung-Shin Ham, Dong-Sik Kim, Woo Cheol Song, Sun U. |
author_facet | Yi, Tac-Ghee Cho, Yun-Kyoung Lee, Hyun-Joo Kim, Junghee Jeon, Myung-Shin Ham, Dong-Sik Kim, Woo Cheol Song, Sun U. |
author_sort | Yi, Tac-Ghee |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs. |
format | Online Article Text |
id | pubmed-6657938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Korean Society for Stem Cell Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-66579382019-07-29 A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells Yi, Tac-Ghee Cho, Yun-Kyoung Lee, Hyun-Joo Kim, Junghee Jeon, Myung-Shin Ham, Dong-Sik Kim, Woo Cheol Song, Sun U. Int J Stem Cells Original Article BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs. Korean Society for Stem Cell Research 2019-06-30 /pmc/articles/PMC6657938/ /pubmed/31242717 http://dx.doi.org/10.15283/ijsc18098 Text en Copyright © 2019 by the Korean Society for Stem Cell Research https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Yi, Tac-Ghee Cho, Yun-Kyoung Lee, Hyun-Joo Kim, Junghee Jeon, Myung-Shin Ham, Dong-Sik Kim, Woo Cheol Song, Sun U. A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title | A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title_full | A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title_fullStr | A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title_full_unstemmed | A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title_short | A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells |
title_sort | novel immunomodulatory mechanism dependent on acetylcholine secreted by human bone marrow-derived mesenchymal stem cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657938/ https://www.ncbi.nlm.nih.gov/pubmed/31242717 http://dx.doi.org/10.15283/ijsc18098 |
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