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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| Format: | Online |
| Language: | English |
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BlackWell Publishing Ltd
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309416/ |
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pubmed-4309416 |
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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 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| 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 |
| spellingShingle |
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 |
| 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 |
| title |
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_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_sort |
mesenchymal stromal cells express garp/lrrc32 on their surface: effects on their biology and immunomodulatory capacity |
| 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 |
| publisher |
BlackWell Publishing Ltd |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309416/ |
| _version_ |
1613181631343886336 |