Modulated expression of adhesion molecules and galectin-1: role during mesenchymal stromal cell immunoregulatory functions.
OBJECTIVE
As mesenchymal stromal cells (MSCs) have been proposed as a tool for management or prevention of graft-vs-host disease, we investigated their immunoregulatory properties, their expression of adhesion molecules and galectin-1, and the impact of environment context on these functions.


METHODS
The effects of MSCs on T-cell proliferation were analyzed using carboxyfluorescein diacetate N-succinimidyl ester labeling. We evaluated the expression of adhesion molecules and galectin-1 by MSCs and the impact of an inflammatory or infectious environment on these expressions. Using neutralizing antibodies against adhesion molecules and a galectin-1 inhibitor, we assessed the role of these molecules in MSC functions.


RESULTS
MSCs inhibition of T-cell proliferation depended on MSC concentrations, cell contact, and culture environment. Expression of adhesion molecules and secretion of galectin-1 by MSCs are tightly regulated. Coculture with activated T cells upregulated expression of CD54 (intercellular adhesion molecule 1) and CD58 (lymphocyte function-associated antigen 3) and secretion of galectin-1 by MSCs. Interestingly, in an inflammatory or infectious environment, expression of adhesion molecules and galectin-1 by MSCs was differentially modulated. Furthermore, blocking galectin-1 activity prevented the suppressive potential of MSCs. Neutralization of adhesion molecule activity had no effect on MSC inhibition.


CONCLUSIONS
Galectin-1 plays an important role in MSC immunoregulatory functions, which are depending on cell environment. The present study provides new insights concerning MSC physiology and will increase the safety and efficiency of MSCs in clinical settings.
Najar
Mehdi
M
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. mnajar@ulb.ac.be
Raicevic
Gordana
G
Id Boufker
Hicham
H
Stamatopoulos
Basile
B
De Bruyn
Cécile
C
Meuleman
Nathalie
N
Bron
Dominique
D
Toungouz
Michel
M
Lagneaux
Laurence
L
D000293:Adolescent; D000328:Adult; D018968:CD58 Antigens / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D037483:Galectin 1 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
D018968:CD58 Antigens; D017077:Culture Media, Conditioned; D037483:Galectin 1; D018799:Intercellular Adhesion Molecule-1