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

Blood. 2010 Nov 11;116(19):3770-9. doi: 10.1182/blood-2010-02-270777. Epub 2010 Jul 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / metabolism
  • DNA Primers / genetics
  • Galectin 1 / antagonists & inhibitors
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Killer Cells, Natural / immunology
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism*
  • Multipotent Stem Cells / immunology*
  • Multipotent Stem Cells / metabolism*
  • Stromal Cells / immunology*
  • Stromal Cells / metabolism*

Substances

  • Cytokines
  • DNA Primers
  • Galectin 1
  • LGALS1 protein, human