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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25highFOXP3+ regulatory T cells
Stem Cells, Volume 26, No. 1, Year 2008
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Description
Adult bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells that are the subject of intense investigation in regenerative medicine. In addition, MSCs possess immunomodulatory properties with therapeutic potential to prevent graft-versus-host disease (GvHD) in allogeneic hematopoietic cell transplantation. Indeed, MSCs can inhibit natural killer (NK) function, modulate dendritic cell maturation, and suppress allogeneic T-cell response. Here, we report that the nonclassic human leukocyte antigen (HLA) class I molecule HLA-G is responsible for the immunomodulatory properties of MSCs. Our data show that MSCs secrete the soluble isoform HLA-G5 and that such secretion is interleukin-10-dependent. Moreover, cell contact between MSCs and allostimulated T cells is required to obtain a full HLA-G5 secretion and, as consequence, a full immunomodulation from MSCs. Blocking experiments using neutralizing anti-HLA-G antibody demonstrate that HLA-G5 contributes first to the suppression of allogeneic T-cell proliferation and then to the expansion of CD4 +CD25highFOXP3+ regulatory T cells. Furthermore, we demonstrate that in addition to their action on the adaptive immune system, MSCs, through HLA-G5, affect innate immunity by inhibiting both NK cell-mediated cytolysis and interferon-γ secretion. Our results provide evidence that HLA-G5 secreted by MSCs is critical to the suppressive functions of MSCs and should contribute to improving clinical therapeutic trials that use MSCs to prevent GvHD. ©AlphaMed Press.
Authors & Co-Authors
Zidi, Inès
France, Paris
Institut de Recherche Saint-louis
Favier, Benoît
France, Paris
Institut de Recherche Saint-louis
Borg, Christophe
France, Saint-denis-la-plaine
Etablissement Français du Sang
Tiberghien, Pierre
France, Saint-denis-la-plaine
Etablissement Français du Sang
Rouas-Freiss, Nathalie
France, Paris
Institut de Recherche Saint-louis
Carosella, Edgardo Delfino
France, Paris
Institut de Recherche Saint-louis
Statistics
Citations: 874
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1634/stemcells.2007-0554
ISSN:
10665099
Research Areas
Cancer
Health System And Policy