title: Galectin-9 is Involved in Immunosuppression Mediated by Human Bone Marrow-derived Clonal Mesenchymal Stem Cells.
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 β-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.
authors.affiliation: Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon 22332, Korea.
authors.forename: Si-Na
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Drug Development Program, Department of Medicine, Inha University School of Medicine, Incheon 22332, Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon 22332, Korea. ; Inha Research Institute for Medical Sciences of Biomedical Sciences, Inha University School of Medicine, Incheon 22332, Korea.
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Jeon
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon 22332, Korea. ; Inha Research Institute for Medical Sciences of Biomedical Sciences, Inha University School of Medicine, Incheon 22332, Korea. ; SCM Lifescience Co. Ltd., Incheon 22332, Korea.
authors.forename: TacGhee
authors.initials: T
authors.lastname: Yi
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon 22332, Korea. ; SCM Lifescience Co. Ltd., Incheon 22332, Korea.
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
keywords: Apoptosis; Galectin-9; Human mesenchymal stem cells; Immunosuppression; TIM-3