Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells
| Autor: | Andrea Blaskó, Ildikó Makra, Nandor Gabor Than, Éva Kriston-Pál, Roberta Fajka-Boja, Ferenc Uher, Enikő Szabó, Ágnes Czibula, Veronika S. Urbán, Éva Monostori, Gábor J. Szebeni, Ákos Hornung |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cancer Research Cell signaling Galectin 1 T-Lymphocytes medicine.medical_treatment Immunology Population Apoptosis Cell Communication Biology Lymphocyte Activation Mice 03 medical and health sciences 0302 clinical medicine Bone Marrow In vivo medicine Animals Immunologic Factors Immunology and Allergy education Cells Cultured Genetics (clinical) Cell Proliferation Mice Knockout Transplantation education.field_of_study Mesenchymal stem cell Mesenchymal Stem Cells Immunosuppression Cell Biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Oncology Galectin-1 Knockout mouse Cancer research Bone marrow Immunosuppressive Agents 030215 immunology |
| Zdroj: | Cytotherapy. 18:360-370 |
| ISSN: | 1465-3249 |
| Popis: | BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. METHODS: MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. RESULTS: Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. CONCLUSIONS: These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target. |
| Databáze: | OpenAIRE |
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