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Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity

Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transformi...

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Autores principales: Carrillo-Galvez, Ana Belén, Cobo, Marién, Cuevas-Ocaña, Sara, Gutiérrez-Guerrero, Alejandra, Sánchez-Gilabert, Almudena, Bongarzone, Pierpaolo, García-Pérez, Angélica, Muñoz, Pilar, Benabdellah, Karim, Toscano, Miguel G, Martín, Francisco, Anderson, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309416/
https://www.ncbi.nlm.nih.gov/pubmed/25182959
http://dx.doi.org/10.1002/stem.1821
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author Carrillo-Galvez, Ana Belén
Cobo, Marién
Cuevas-Ocaña, Sara
Gutiérrez-Guerrero, Alejandra
Sánchez-Gilabert, Almudena
Bongarzone, Pierpaolo
García-Pérez, Angélica
Muñoz, Pilar
Benabdellah, Karim
Toscano, Miguel G
Martín, Francisco
Anderson, Per
author_facet Carrillo-Galvez, Ana Belén
Cobo, Marién
Cuevas-Ocaña, Sara
Gutiérrez-Guerrero, Alejandra
Sánchez-Gilabert, Almudena
Bongarzone, Pierpaolo
García-Pérez, Angélica
Muñoz, Pilar
Benabdellah, Karim
Toscano, Miguel G
Martín, Francisco
Anderson, Per
author_sort Carrillo-Galvez, Ana Belén
collection PubMed
description Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine involved in MSC migration, differentiation, and immunomodulation. Recently, glycoprotein A repetitions predominant (GARP) was shown to bind latency-associated peptide (LAP)/TGF-β1 to the cell surface of activated Foxp3(+) regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF-β1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF-β1 and reduced their proliferative capacity in a TGF-β1-independent manner. Importantly, we showed that GARP expression on MSCs contributed to their ability to inhibit T-cell responses in vitro. In summary, we have found that GARP is an essential molecule for MSC biology, regulating their immunomodulatory and proliferative activities. We envision GARP as a new target for improving the therapeutic efficacy of MSCs and also as a novel MSC marker. Stem Cells 2015;33:183–195
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spelling pubmed-43094162015-02-09 Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity Carrillo-Galvez, Ana Belén Cobo, Marién Cuevas-Ocaña, Sara Gutiérrez-Guerrero, Alejandra Sánchez-Gilabert, Almudena Bongarzone, Pierpaolo García-Pérez, Angélica Muñoz, Pilar Benabdellah, Karim Toscano, Miguel G Martín, Francisco Anderson, Per Stem Cells Tissue-Specific Stem Cells Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine involved in MSC migration, differentiation, and immunomodulation. Recently, glycoprotein A repetitions predominant (GARP) was shown to bind latency-associated peptide (LAP)/TGF-β1 to the cell surface of activated Foxp3(+) regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF-β1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF-β1 and reduced their proliferative capacity in a TGF-β1-independent manner. Importantly, we showed that GARP expression on MSCs contributed to their ability to inhibit T-cell responses in vitro. In summary, we have found that GARP is an essential molecule for MSC biology, regulating their immunomodulatory and proliferative activities. We envision GARP as a new target for improving the therapeutic efficacy of MSCs and also as a novel MSC marker. Stem Cells 2015;33:183–195 BlackWell Publishing Ltd 2015-01 2014-12-18 /pmc/articles/PMC4309416/ /pubmed/25182959 http://dx.doi.org/10.1002/stem.1821 Text en © 2014 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Tissue-Specific Stem Cells
Carrillo-Galvez, Ana Belén
Cobo, Marién
Cuevas-Ocaña, Sara
Gutiérrez-Guerrero, Alejandra
Sánchez-Gilabert, Almudena
Bongarzone, Pierpaolo
García-Pérez, Angélica
Muñoz, Pilar
Benabdellah, Karim
Toscano, Miguel G
Martín, Francisco
Anderson, Per
Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title_full Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title_fullStr Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title_full_unstemmed Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title_short Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
title_sort mesenchymal stromal cells express garp/lrrc32 on their surface: effects on their biology and immunomodulatory capacity
topic Tissue-Specific Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309416/
https://www.ncbi.nlm.nih.gov/pubmed/25182959
http://dx.doi.org/10.1002/stem.1821
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