Journal
STEM CELLS AND DEVELOPMENT
Volume 28, Issue 1, Pages 44-55Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2018.0015
Keywords
MSC; exosomes; NK cells; TGF beta
Funding
- Groupe Collaboratif en Transplantation d'Ile de France (GCIF)
- Institut Francilien de Recherche en Nephrologie et Transplantation (IFRNT)
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Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer (NK) cells, through cell-cell contact or secreted factors. Exosomes secreted by MSCs may be involved in their regulatory functions, providing new therapeutic tools. Here, we showed that fetal liver (FL) MSC-derived exosomes inhibit proliferation, activation, and cytotoxicity of NK cells. Exosomes bearing latency associated peptide (LAP), TGF beta, and thrombospondin 1 (TSP1), a regulatory molecule for TGF beta, induced downstream TGF beta/Smad2/3 signaling in NK cells. The inhibition of TGF beta, using a neutralizing anti-TGF beta antibody, restored NK proliferation, differentiation, and cytotoxicity, demonstrating that FL-MSC-derived exosomes exert their inhibition on NK cell function via TGF beta. These results suggest that FL-MSC-derived exosomes regulate NK cell functions through exosome-associated TGF beta.
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