Human multipotent mesenchymal stromal cells (MSC) suppress proliferation and alloreactivity of T cells. Several signalling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated if lectins are involved in immune modulation by MSC. Gene expression profiling of MSC revealed that one of the most important lectins in this setting, galectin-1, was highly expressed. Galectin-1 protein was detected intracellularly and on the cell surface of MSC. In addition, galectin-1 was released into the cell culture supernatant by MSC. In order to analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSC using a retroviral transfection system was established. Galectin-1 knockdown in MSC resulted in a significant loss of their immunomodulatory properties, when compared to MSC infected with non-targeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4(+) and CD8(+) T cells. By contrast, the effect of MSC on non-alloreactive NK cells was unaffected by downregulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in GvHD and autoimmunity, e. g. TNFalpha, IFNgamma, IL-2 and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSC on allogeneic T cells.

Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells / F., Gieseke; J., Böhringer; Bussolari, Rita; Dominici, Massimo; R., Handgretinger; I., Müller. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 116:(2010), pp. 3770-3779. [10.1182/blood-2010-02-270777]

Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells

BUSSOLARI, Rita;DOMINICI, Massimo;
2010

Abstract

Human multipotent mesenchymal stromal cells (MSC) suppress proliferation and alloreactivity of T cells. Several signalling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated if lectins are involved in immune modulation by MSC. Gene expression profiling of MSC revealed that one of the most important lectins in this setting, galectin-1, was highly expressed. Galectin-1 protein was detected intracellularly and on the cell surface of MSC. In addition, galectin-1 was released into the cell culture supernatant by MSC. In order to analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSC using a retroviral transfection system was established. Galectin-1 knockdown in MSC resulted in a significant loss of their immunomodulatory properties, when compared to MSC infected with non-targeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4(+) and CD8(+) T cells. By contrast, the effect of MSC on non-alloreactive NK cells was unaffected by downregulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in GvHD and autoimmunity, e. g. TNFalpha, IFNgamma, IL-2 and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSC on allogeneic T cells.
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Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells / F., Gieseke; J., Böhringer; Bussolari, Rita; Dominici, Massimo; R., Handgretinger; I., Müller. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 116:(2010), pp. 3770-3779. [10.1182/blood-2010-02-270777]
F., Gieseke; J., Böhringer; Bussolari, Rita; Dominici, Massimo; R., Handgretinger; I., Müller
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/646520
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