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Mesenchymal stem cells: a double-edged sword in regulating immune responses
Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted ac...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422473/ https://www.ncbi.nlm.nih.gov/pubmed/22421969 http://dx.doi.org/10.1038/cdd.2012.26 |
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author | Li, W Ren, G Huang, Y Su, J Han, Y Li, J Chen, X Cao, K Chen, Q Shou, P Zhang, L Yuan, Z-R Roberts, A I Shi, S Le, A D Shi, Y |
author_facet | Li, W Ren, G Huang, Y Su, J Han, Y Li, J Chen, X Cao, K Chen, Q Shou, P Zhang, L Yuan, Z-R Roberts, A I Shi, S Le, A D Shi, Y |
author_sort | Li, W |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS(−/−) MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5(−/−)CXCR3(−/−) mice, the immune-promoting effect of iNOS(−/−) MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs. |
format | Online Article Text |
id | pubmed-3422473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-34224732012-09-01 Mesenchymal stem cells: a double-edged sword in regulating immune responses Li, W Ren, G Huang, Y Su, J Han, Y Li, J Chen, X Cao, K Chen, Q Shou, P Zhang, L Yuan, Z-R Roberts, A I Shi, S Le, A D Shi, Y Cell Death Differ Original Paper Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS(−/−) MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5(−/−)CXCR3(−/−) mice, the immune-promoting effect of iNOS(−/−) MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs. Nature Publishing Group 2012-09 2012-03-16 /pmc/articles/PMC3422473/ /pubmed/22421969 http://dx.doi.org/10.1038/cdd.2012.26 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Paper Li, W Ren, G Huang, Y Su, J Han, Y Li, J Chen, X Cao, K Chen, Q Shou, P Zhang, L Yuan, Z-R Roberts, A I Shi, S Le, A D Shi, Y Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title | Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title_full | Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title_fullStr | Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title_full_unstemmed | Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title_short | Mesenchymal stem cells: a double-edged sword in regulating immune responses |
title_sort | mesenchymal stem cells: a double-edged sword in regulating immune responses |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422473/ https://www.ncbi.nlm.nih.gov/pubmed/22421969 http://dx.doi.org/10.1038/cdd.2012.26 |
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