期刊
STEM CELLS
卷 33, 期 1, 页码 183-195出版社
WILEY
DOI: 10.1002/stem.1821
关键词
Glycoprotein A repetitions predominant; Leucine-rich repeat containing 32; Mesenchymal stem cells; Membrane bound TGF-beta 1; Proliferation; Immunomodulation
资金
- Fondo de Investigaciones Sanitarias ISCIII (Spain)
- Fondo Europeo de Desarrollo Regional (FEDER) from the European Union [NPI12/01390, NPI12/01097]
- ISCIII Red de Terapia Celular [RD12/0019/0006]
- Consejeria de Innovacion Ciencia y Empresa [NP09CTS- 04532]
- Junta de Andalucia and FEDER/Fondo de Cohesion Europeo (FSE) de Andalucia [NPI0001/2009]
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)-beta 1 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-beta 1 to the cell surface of activated Foxp3 1 regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF-beta 1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF-beta 1 and reduced their proliferative capacity in a TGF-beta 1-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据