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Topics {✒️}

hmgb1/pten/β-catenin axis hepatocyte growth factor hua-ling wang enzyme-linked immunosorbent assay article download pdf han-bing chen rui-qiang zheng chemical-induced liver injury th17/treg cell balance th17/treg cell differentiation phosphatidylinositol-3 kinase/akt pathway mesenchymal stem cells anti-inflammatory factors partly th17/treg cell ratio tiam1/rac-dependent inhibition treg cell-related cytokines impact cell therapy full access msc number-dependent manner exert anti-inflammatory effects extracellular vesicles derived transcription factor foxp3 cell subset-specific markers cd4+cd25+foxp3+ cells cd4+cd3+rorrt+ cells msc growth medium research quality control cd4+cd3+rorγt+ cells stem cells int treg/th17 balance th17/treg balance privacy choices/manage cookies tgf-β mrna expression inhibit neutrophil phagocytic bone-marrow article chen acute lung injury systemic inflammatory responses related subjects increased lung permeability monocyte isolation kit th17/treg cells acute pulmonary inflammation cytokine mrna expression cell cytokine expression single-cell suspension anti-inflammatory factors obtain permission directly cell culture inserts intensive care med

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         headline:Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro
         description:Mesenchymal stem cells (MSCs) exert immunomodulatory functions by inducing the development and differentiation of naive T cells into T cells with an anti-inflammatory regulatory T cell (Treg) phenotype. Our previous study showed that hepatocyte growth factor (HGF) secreted by MSCs had immunomodulatory effects in the context of lipopolysaccharide (LPS) stimulation. We hypothesized that HGF is a key factor in the MSC-mediated regulation of the T helper 17 (Th17) cell/regulatory T (Treg) cell balance. We investigated the effects of MSCs on the differentiation of CD4+ T cells and the functions of Th17/Treg cells in response to LPS stimulation by performing in vitro coculture experiments. MSCs were added to the upper chambers of cell culture inserts, and CD4+ T cells were plated in the lower chambers, followed by treatment with LPS or an anti-HGF antibody. Th17 (CD4+CD3+RORrt+) and Treg (CD4+CD25+Foxp3+) cell frequencies were analysed by flow cytometry, and the expression of Th17 cell- and Treg cell-related cytokines in the CD4+ T cells or culture medium was measured by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophil functions were determined by flow cytometry after a coculture with Th17/Treg cells. The percentage of CD4+CD25+Foxp3+ cells was significantly increased in the CD4+ T cell population, while the percentage of CD4+CD3+RORrt+ cells was significantly decreased after MSC coculture. However, the MSC-induced effect was significantly inhibited by the anti-HGF antibody (p < 0.05). Furthermore, MSCs significantly inhibited the CD4+ T cell expression of IL-17 and IL-6 but increased the expression of IL-10 (p < 0.05 or p < 0.01); these effects were inhibited by the anti-HGF antibody (p < 0.05). In addition, CD4+ T cells cocultured with MSCs significantly inhibited neutrophil phagocytic and oxidative burst activities (p < 0.05 or p < 0.01); however, these MSC-induced effects were inhibited by the anti-HGF antibody (p < 0.05). These data suggested that MSCs induced the conversion of fully differentiated Th17 cells into functional Treg cells and thereby modulated the Th17/Treg cell balance in the CD4+ T cell population, which was partly attributed to HGF secreted by the MSCs.
         datePublished:2020-02-28T00:00:00Z
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            Cell Biology
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      headline:Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro
      description:Mesenchymal stem cells (MSCs) exert immunomodulatory functions by inducing the development and differentiation of naive T cells into T cells with an anti-inflammatory regulatory T cell (Treg) phenotype. Our previous study showed that hepatocyte growth factor (HGF) secreted by MSCs had immunomodulatory effects in the context of lipopolysaccharide (LPS) stimulation. We hypothesized that HGF is a key factor in the MSC-mediated regulation of the T helper 17 (Th17) cell/regulatory T (Treg) cell balance. We investigated the effects of MSCs on the differentiation of CD4+ T cells and the functions of Th17/Treg cells in response to LPS stimulation by performing in vitro coculture experiments. MSCs were added to the upper chambers of cell culture inserts, and CD4+ T cells were plated in the lower chambers, followed by treatment with LPS or an anti-HGF antibody. Th17 (CD4+CD3+RORrt+) and Treg (CD4+CD25+Foxp3+) cell frequencies were analysed by flow cytometry, and the expression of Th17 cell- and Treg cell-related cytokines in the CD4+ T cells or culture medium was measured by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophil functions were determined by flow cytometry after a coculture with Th17/Treg cells. The percentage of CD4+CD25+Foxp3+ cells was significantly increased in the CD4+ T cell population, while the percentage of CD4+CD3+RORrt+ cells was significantly decreased after MSC coculture. However, the MSC-induced effect was significantly inhibited by the anti-HGF antibody (p < 0.05). Furthermore, MSCs significantly inhibited the CD4+ T cell expression of IL-17 and IL-6 but increased the expression of IL-10 (p < 0.05 or p < 0.01); these effects were inhibited by the anti-HGF antibody (p < 0.05). In addition, CD4+ T cells cocultured with MSCs significantly inhibited neutrophil phagocytic and oxidative burst activities (p < 0.05 or p < 0.01); however, these MSC-induced effects were inhibited by the anti-HGF antibody (p < 0.05). These data suggested that MSCs induced the conversion of fully differentiated Th17 cells into functional Treg cells and thereby modulated the Th17/Treg cell balance in the CD4+ T cell population, which was partly attributed to HGF secreted by the MSCs.
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         Th17
         Treg
         Hepatocyte growth factor
         Stem Cells
         Cell Biology
         Regenerative Medicine/Tissue Engineering
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      name:Department of Critical Care Medicine, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, People’s Republic of China
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      name:Department of Cardiology, Northern Jiangsu People’s Hospital & Jiangdu People’s Hospital of Yangzhou, Yangzhou, People’s Republic of China
      name:Department of Critical Care Medicine, Jiangdu People’s Hospital of Yangzhou, Jiangdu People’s Hospital Affiliated with the Medical College of Yangzhou University, Yangzhou, People’s Republic of China

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