title: Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study.
  
  
  METHODS
  MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity.
  
  
  RESULTS
  Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect.
  
  
  CONCLUSIONS
  These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target.
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Roberta
authors: R
authors: Fajka-Boja
authors: Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary; Stem Cell Biology, National Blood Service, Budapest, Hungary.
authors: Veronika S
authors: VS
authors: Urbán
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Gábor J
authors: GJ
authors: Szebeni
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Ágnes
authors: Á
authors: Czibula
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Andrea
authors: A
authors: Blaskó
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Éva
authors: É
authors: Kriston-Pál
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; SZTE-MTA Lendület Foldamer Research Group, University of Szeged, H-6720 Szeged, Hungary.
authors: Ildikó
authors: I
authors: Makra
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; Department of Rheumatology, University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Health Centre, Szeged, Hungary.
authors: Ákos
authors: Á
authors: Hornung
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors: Enikő
authors: E
authors: Szabó
authors: Stem Cell Biology, National Blood Service, Budapest, Hungary.
authors: Ferenc
authors: F
authors: Uher
authors: Lendulet Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors: Nándor G
authors: NG
authors: Than
authors: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. Electronic address: monostori.eva@brc.mta.hu.
authors: Éva
authors: É
authors: Monostori
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D037483:Galectin 1 / Q000235:genetics / Q000502:physiology*; D007155:Immunologic Factors / Q000235:genetics / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D037483:Galectin 1; D007155:Immunologic Factors; D007166:Immunosuppressive Agents
keywords: apoptosis; delayed type hypersensitivity; galectin-1; immunosuppression; mesenchymal stromal cells; type I diabetes