Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1
Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocyt...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/6516854 |
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| author | Yury Rubtsov Кirill Goryunov Аndrey Romanov Yulia Suzdaltseva George Sharonov Vsevolod Tkachuk |
| author_facet | Yury Rubtsov Кirill Goryunov Аndrey Romanov Yulia Suzdaltseva George Sharonov Vsevolod Tkachuk |
| author_sort | Yury Rubtsov |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rα that negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration. |
| format | Article |
| id | doaj-art-9be51f3836de4ee7b904e6c409aa91ef |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-9be51f3836de4ee7b904e6c409aa91ef2025-02-03T05:54:39ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/65168546516854Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1Yury Rubtsov0Кirill Goryunov1Аndrey Romanov2Yulia Suzdaltseva3George Sharonov4Vsevolod Tkachuk5Department of Medicine, Lomonosov Moscow State University, Lomonosovsky prospect 27-1, Moscow 119192, RussiaDepartment of Medicine, Lomonosov Moscow State University, Lomonosovsky prospect 27-1, Moscow 119192, RussiaDepartment of Medicine, Lomonosov Moscow State University, Lomonosovsky prospect 27-1, Moscow 119192, RussiaRussian Cardiology Research and Production Complex, 3-rd Cherepkovskaya str. 15-a, Moscow 11552, RussiaDepartment of Medicine, Lomonosov Moscow State University, Lomonosovsky prospect 27-1, Moscow 119192, RussiaDepartment of Medicine, Lomonosov Moscow State University, Lomonosovsky prospect 27-1, Moscow 119192, RussiaMesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rα that negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration.http://dx.doi.org/10.1155/2017/6516854 |
| spellingShingle | Yury Rubtsov Кirill Goryunov Аndrey Romanov Yulia Suzdaltseva George Sharonov Vsevolod Tkachuk Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 Stem Cells International |
| title | Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 |
| title_full | Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 |
| title_fullStr | Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 |
| title_full_unstemmed | Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 |
| title_short | Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1 |
| title_sort | molecular mechanisms of immunomodulation properties of mesenchymal stromal cells a new insight into the role of icam 1 |
| url | http://dx.doi.org/10.1155/2017/6516854 |
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