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PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties

Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use i...

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Autores principales: Contreras-Lopez, R. A., Elizondo-Vega, R., Torres, M. J., Vega-Letter, A. M., Luque-Campos, N., Paredes-Martinez, M. J., Pradenas, C., Tejedor, G., Oyarce, K., Salgado, M., Jorgensen, C., Khoury, M., Kronke, G., Garcia-Robles, M. A., Altamirano, C., Luz-Crawford, P., Djouad, F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351754/
https://www.ncbi.nlm.nih.gov/pubmed/32651456
http://dx.doi.org/10.1038/s41598-020-68347-x
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author Contreras-Lopez, R. A.
Elizondo-Vega, R.
Torres, M. J.
Vega-Letter, A. M.
Luque-Campos, N.
Paredes-Martinez, M. J.
Pradenas, C.
Tejedor, G.
Oyarce, K.
Salgado, M.
Jorgensen, C.
Khoury, M.
Kronke, G.
Garcia-Robles, M. A.
Altamirano, C.
Luz-Crawford, P.
Djouad, F.
author_facet Contreras-Lopez, R. A.
Elizondo-Vega, R.
Torres, M. J.
Vega-Letter, A. M.
Luque-Campos, N.
Paredes-Martinez, M. J.
Pradenas, C.
Tejedor, G.
Oyarce, K.
Salgado, M.
Jorgensen, C.
Khoury, M.
Kronke, G.
Garcia-Robles, M. A.
Altamirano, C.
Luz-Crawford, P.
Djouad, F.
author_sort Contreras-Lopez, R. A.
collection PubMed
description Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARβ/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARβ/δ on MSC metabolic activity and the relevance of PPARβ/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARβ/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARβ/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARβ/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.
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spelling pubmed-73517542020-07-14 PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties Contreras-Lopez, R. A. Elizondo-Vega, R. Torres, M. J. Vega-Letter, A. M. Luque-Campos, N. Paredes-Martinez, M. J. Pradenas, C. Tejedor, G. Oyarce, K. Salgado, M. Jorgensen, C. Khoury, M. Kronke, G. Garcia-Robles, M. A. Altamirano, C. Luz-Crawford, P. Djouad, F. Sci Rep Article Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARβ/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARβ/δ on MSC metabolic activity and the relevance of PPARβ/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARβ/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARβ/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARβ/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility. Nature Publishing Group UK 2020-07-10 /pmc/articles/PMC7351754/ /pubmed/32651456 http://dx.doi.org/10.1038/s41598-020-68347-x Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Contreras-Lopez, R. A.
Elizondo-Vega, R.
Torres, M. J.
Vega-Letter, A. M.
Luque-Campos, N.
Paredes-Martinez, M. J.
Pradenas, C.
Tejedor, G.
Oyarce, K.
Salgado, M.
Jorgensen, C.
Khoury, M.
Kronke, G.
Garcia-Robles, M. A.
Altamirano, C.
Luz-Crawford, P.
Djouad, F.
PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title_full PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title_fullStr PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title_full_unstemmed PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title_short PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties
title_sort pparβ/δ-dependent msc metabolism determines their immunoregulatory properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351754/
https://www.ncbi.nlm.nih.gov/pubmed/32651456
http://dx.doi.org/10.1038/s41598-020-68347-x
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