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Stem Cells. 2015 Jan;33(1):183-95. doi: 10.1002/stem.1821.

Mesenchymal stromal cells express GARP/LRRC32 on their surface: effects on their biology and immunomodulatory capacity.

Author information

1
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalucian Regional Government, PTS Granada, Granada, Spain.

Abstract

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.

KEYWORDS:

Glycoprotein A repetitions predominant; Immunomodulation; Leucine-rich repeat containing 32; Membrane bound TGF-β1; Mesenchymal stem cells; Proliferation

PMID:
25182959
PMCID:
PMC4309416
DOI:
10.1002/stem.1821
[Indexed for MEDLINE]
Free PMC Article
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