Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
| Autor: | Ana Belén Carrillo-Gálvez, Almudena Sánchez-Gilabert, Marién Cobo, Per Anderson, Karim Benabdellah, Pilar Muñoz, Sara Cuevas‐Ocaña, Francisco Martin, Miguel G. Toscano, Alejandra Gutierrez-Guerrero, Angélica García-Pérez, Pierpaolo Bongarzone |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Cellular differentiation medicine.medical_treatment Proliferation Biology Regenerative medicine Immunomodulation Mice medicine Animals Humans Tissue-Specific Stem Cells Cell Proliferation Mice Inbred BALB C Mesenchymal stem cell Membrane bound TGF-β1 FOXP3 Membrane Proteins Cell Differentiation Mesenchymal Stem Cells Cell Biology Cell biology Transplantation Leucine-rich repeat containing 32 Cytokine Glycoprotein A repetitions predominant Molecular Medicine Stem cell Developmental Biology Transforming growth factor |
| Zdroj: | Stem Cells (Dayton, Ohio) |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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