Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells
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Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. / Gieseke, Friederike; Böhringer, Judith; Bussolari, Rita; Dominici, Massimo; Handgretinger, Rupert; Müller, Ingo.
In: BLOOD, Vol. 116, No. 19, 11.11.2010, p. 3770-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Transfer › peer-review
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TY - JOUR
T1 - Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells
AU - Gieseke, Friederike
AU - Böhringer, Judith
AU - Bussolari, Rita
AU - Dominici, Massimo
AU - Handgretinger, Rupert
AU - Müller, Ingo
PY - 2010/11/11
Y1 - 2010/11/11
N2 - Human multipotent mesenchymal stromal cells (MSCs) suppress proliferation and alloreactivity of T cells. Several signaling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated whether lectins are involved in immune modulation by MSC. Gene expression profiling of MSCs 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 MSCs. In addition, galectin-1 was released into the cell culture supernatant by MSCs. To analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSCs with use of a retroviral transfection system was established. Galectin-1 knockdown in MSCs resulted in a significant loss of their immunomodulatory properties, compared with MSCs infected with nontargeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4(+) and CD8(+) T cells. By contrast, the effect of MSCs on nonalloreactive natural killer (NK) cells was unaffected by down-regulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in graft-versus-host disease (GVHD) and autoimmunity (eg, tumor necrosis factor-α [TNFα], IFNγ, interleukin-2 [IL-2], and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSCs on allogeneic T cells.
AB - Human multipotent mesenchymal stromal cells (MSCs) suppress proliferation and alloreactivity of T cells. Several signaling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated whether lectins are involved in immune modulation by MSC. Gene expression profiling of MSCs 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 MSCs. In addition, galectin-1 was released into the cell culture supernatant by MSCs. To analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSCs with use of a retroviral transfection system was established. Galectin-1 knockdown in MSCs resulted in a significant loss of their immunomodulatory properties, compared with MSCs infected with nontargeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4(+) and CD8(+) T cells. By contrast, the effect of MSCs on nonalloreactive natural killer (NK) cells was unaffected by down-regulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in graft-versus-host disease (GVHD) and autoimmunity (eg, tumor necrosis factor-α [TNFα], IFNγ, interleukin-2 [IL-2], and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSCs on allogeneic T cells.
KW - Base Sequence
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Cell Proliferation
KW - Cells, Cultured
KW - Coculture Techniques
KW - Cytokines
KW - DNA Primers
KW - Galectin 1
KW - Gene Expression
KW - Gene Knockdown Techniques
KW - Humans
KW - Killer Cells, Natural
KW - Mesenchymal Stromal Cells
KW - Multipotent Stem Cells
KW - Stromal Cells
U2 - 10.1182/blood-2010-02-270777
DO - 10.1182/blood-2010-02-270777
M3 - SCORING: Journal article
C2 - 20644118
VL - 116
SP - 3770
EP - 3779
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 19
ER -