We are analyzing https://link.springer.com/article/10.1186/s13287-015-0021-5.

Title:
Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells | Stem Cell Research & Therapy
Description:
Introduction Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition of dendritic cell (DC) maturation involving both cell contact and soluble factors. These properties have made MSC attractive candidates for cellular therapy. However, the mechanism underlying these characteristics remains unclear. This study sought to investigate the mechanisms by which MSC induce a regulatory environment. Method Allogeneic bone marrow mesenchymal stromal cells were cultured with T cells or dendritic cells in the presence or absence of gamma secretase inhibitor to block Notch receptor signalling. T cells and dendritic cells were examined by flow cytometry for changes in phenotype marker expression. Stable knock down MSC were generated to examine the influence of Jagged 1 signalling by MSC. Both wildtype and knockdown MSC were subsequently used in vivo in an animal model of allergic airway inflammation. Results The Notch ligand Jagged-1 was demonstrated to be involved in MSC expansion of regulatory T cells (Treg). Additionally, MSC-induced a functional semi-mature DC phenotype, which further required Notch signalling for the expansion of Treg. MSC, but not Jagged-1 knock down MSC, reduced pathology in a mouse model of allergic airway inflammation. Protection mediated by MSC was associated with enhanced Treg in the lung and significantly increased production of interleukin (IL)-10 in splenocytes re-stimulated with allergen. Significantly less Treg and IL-10 was observed in mice treated with Jagged-1 knock down MSC. Conclusions The current study suggests that MSC-mediated immune modulation involves the education and expansion of regulatory immune cells in a Jagged-1 dependent manner and provides the first report of the importance of Jagged-1 signalling in MSC protection against inflammation in vivo.
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Keywords {🔍}

msc, cells, treg, jagged, notch, cell, pubmed, article, google, scholar, cas, regulatory, signalling, expression, mesenchymal, stem, expansion, foxp, dendritic, figure, data, proliferation, role, cultured, knock, induction, immunol, human, mice, ova, allogeneic, presence, hours, bone, vivo, allergic, inflammation, gsi, population, ligand, induce, immune, tdc, studies, control, tolerogenic, examined, airway, additional, required,

Topics {✒️}

s-phenylglycine t-butyl ester major histocompatibility complex monocyte-derived dendritic cells magnetic-activated cell sorting article download pdf t-cell modulatory activity induce t-cell unresponsiveness mesenchymal stromal cells hydrocortisone-treated dendritic cells health research board mahon & karen english mesenchymal stem cells expand cd4+foxp3+cd25+ treg lps-treated dendritic cells regulatory t-cell generation grant number 09/src/b1794 antigen-processing dendritic cells allergen-driven airway pathology research ethics committee semi-quantitative scoring system il-10-treated dendritic cells allogeneic wild-type msc membrane-bound tgf-beta i-eα peptide cell-contact mediated suppression suppress allergic responses bone marrow cells anti-inflammatory cytokines karen english induce cd4 + cd25highfoxp3+ regulatory tolerogenic dendritic cells cd4+ cd25+ foxp3-gpf+ mhc class ii wild-type msc supported msc-mediated immune regulation �semi-mature’ phenotype capable egfp-foxp3 transgenic mice important pre-clinical data open biosystems-thermo cd4+cd25−foxp3− cells notch/jagged family mrna privacy choices/manage cookies antigen-presenting cells author information authors full size image regulatory dendritic cells sorted foxp3-egfp− cd25− untreated ova-sensitized mice cd4+ cd25− foxp3-gfp− multiple experimental groups

Schema {🗺️}

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         description:Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition of dendritic cell (DC) maturation involving both cell contact and soluble factors. These properties have made MSC attractive candidates for cellular therapy. However, the mechanism underlying these characteristics remains unclear. This study sought to investigate the mechanisms by which MSC induce a regulatory environment. Allogeneic bone marrow mesenchymal stromal cells were cultured with T cells or dendritic cells in the presence or absence of gamma secretase inhibitor to block Notch receptor signalling. T cells and dendritic cells were examined by flow cytometry for changes in phenotype marker expression. Stable knock down MSC were generated to examine the influence of Jagged 1 signalling by MSC. Both wildtype and knockdown MSC were subsequently used in vivo in an animal model of allergic airway inflammation. The Notch ligand Jagged-1 was demonstrated to be involved in MSC expansion of regulatory T cells (Treg). Additionally, MSC-induced a functional semi-mature DC phenotype, which further required Notch signalling for the expansion of Treg. MSC, but not Jagged-1 knock down MSC, reduced pathology in a mouse model of allergic airway inflammation. Protection mediated by MSC was associated with enhanced Treg in the lung and significantly increased production of interleukin (IL)-10 in splenocytes re-stimulated with allergen. Significantly less Treg and IL-10 was observed in mice treated with Jagged-1 knock down MSC. The current study suggests that MSC-mediated immune modulation involves the education and expansion of regulatory immune cells in a Jagged-1 dependent manner and provides the first report of the importance of Jagged-1 signalling in MSC protection against inflammation in vivo.
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