Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells

• Published in: Cytotherapy (Oxford, England) Vol. 18; no. 3; pp. 360 - 370
• Main Authors: Fajka-Boja, Roberta, Urbán, Veronika S, Szebeni, Gábor J, Czibula, Ágnes, Blaskó, Andrea, Kriston-Pál, Éva, Makra, Ildikó, Hornung, Ákos, Szabó, Enikő, Uher, Ferenc, Than, Nándor G, Monostori, Éva
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2016
• Subjects: Advanced Basic Science; Animals; apoptosis; Apoptosis - genetics; Bone Marrow - metabolism; Cell Communication - genetics; Cell Proliferation - genetics; Cells, Cultured; delayed type hypersensitivity; Galectin 1 - genetics; Galectin 1 - physiology; galectin-1; Immunologic Factors - genetics; Immunologic Factors - physiology; immunosuppression; Immunosuppressive Agents - metabolism; Lymphocyte Activation - genetics; Male; mesenchymal stromal cells; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Other; T-Lymphocytes - immunology; type I diabetes; apoptosis; immunosuppression; type I diabetes; mesenchymal stromal cells; delayed type hypersensitivity; galectin-1
• DOI: 10.1016/j.jcyt.2015.12.004
• ISSN: 1465-3249

Abstract 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.