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

Abstract

FOXP3؉ 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-␥ 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. STEM CELLS 2008;26:212-222 Disclosure of potential conflicts of interest is found at the end of this article.

Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6

“…Many reports indicate that MSC need to be activated in order to exert their immunomodulatory activities or to produce IL-10. 26,33,34 Our data clearly show that activation of MSC is not required for the IL-10 induction in monocytes.…”

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

“…MSCs alter NK cell phenotype, suppress cytokine-induced proliferation of NK cells and prevent the induction of effector functions [56,57]. MSCs inhibit both NK cell-mediated cytolysis and interferon-gamma secretion [41]. The inhibition of NK cell function is thought to be critical to the suppressive functions of MSCs, especially in therapeutic arenas such as graft-versus-host disease [41].…”

“…MSCs inhibit both NK cell-mediated cytolysis and interferon-gamma secretion [41]. The inhibition of NK cell function is thought to be critical to the suppressive functions of MSCs, especially in therapeutic arenas such as graft-versus-host disease [41].…”

Identification of a novel HLA-G+ regulatory population in blood: expansion after allogeneic transplantation and de novo HLA-G expression at graft-versus-host disease sites

“…To date, no orthologs of HLA-G have been identified in other species, meaning that this concept cannot be proved in in vivo experiments. Of note, mesenchymal stem cells which are used for prevention and treatment of GvHD in humans have been shown to exert an immunosuppressive action through HLA-G. 42 The mechanisms of post-transplant HLA-G upregulation in immune cells and in epithelium remain unclear. In this context, various drugs such as hypomethylating agents have been shown to induce HLA-G expression in vitro.…”