Immune Netw.  2015 Oct;15(5):241-251. 10.4110/in.2015.15.5.241.

Galectin-9 is Involved in Immunosuppression Mediated by Human Bone Marrow-derived Clonal Mesenchymal Stem Cells

Affiliations
  • 1Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon 22332, Korea.
  • 2Translational Research Center, Inha University School of Medicine, Incheon 22332, Korea. sunuksong@inha.ac.kr, tgwise@inha.ac.kr
  • 3Inha Research Institute for Medical Sciences of Biomedical Sciences, Inha University School of Medicine, Incheon 22332, Korea.
  • 4SCM Lifescience Co. Ltd., Incheon 22332, Korea.

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) have immunomodulatory properties and can suppress exaggerated pro-inflammatory immune responses. Although the exact mechanisms remain unclear, a variety of soluble factors are known to contribute to MSC-mediated immunosuppression. However, functional redundancy in the immunosuppressive properties of MSCs indicates that other uncharacterized factors could be involved. Galectin-9, a member of the beta-galactoside binding galectin family, has emerged as an important regulator of innate and adaptive immunity. We examined whether galectin-9 contributes to MSC-mediated immunosuppression. Galectin-9 was strongly induced and secreted from human MSCs upon stimulation with pro-inflammatory cytokines. An in vitro immunosuppression assay using a knockdown approach revealed that galectin-9-deficient MSCs do not exert immunosuppressive activity. We also provided evidence that galectin-9 may contribute to MSC-mediated immunosuppression by binding to its receptor, TIM-3, expressed on activated lymphocytes, leading to apoptotic cell death of activated lymphocytes. Taken together, our findings demonstrate that galectin-9 is involved in MSC-mediated immunosuppression and represents a potential therapeutic factor for the treatment of inflammatory diseases.

Keyword

Human mesenchymal stem cells; Immunosuppression; Galectin-9; Apoptosis; TIM-3

MeSH Terms

Adaptive Immunity
Apoptosis
Cell Death
Cytokines
Galectins
Humans*
Immunosuppression*
Lymphocytes
Mesenchymal Stromal Cells*
Cytokines
Galectins
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