Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources.
Due to their immunomodulatory properties, adipose tissue (AT) and Wharton's Jelly (WJ) constitute valuable alternatives to BM as sources of MSCs for managing graft-versus-host disease. To ensure the efficiency of AT- and WJ-MSCs implies the characterization of their immunomodulatory functions in comparison to those of BM. In this study, we investigated the capacity of AT- and WJ-MSCs to modulate lymphocyte reactions in response to different stimuli as well as the specificity of this immunomodulation. AT- and WJ-MSC displayed potent immunosuppressive effects on lymphocyte responses in a dose-dependent manner. These effects included the prevention of lymphocyte activation as well as the suppression of T-cell proliferation regardless of the stimuli used to activate lymphocytes. These effects were mediated through the expression of COX1/COX2 enzymes and by the production of PGE2. CD4(+) and CD8(+) T-lymphocytes were equally targeted by MSCs demonstrating that the immunomodulation was not restricted to a specific T-cell subpopulation.
Najar
Mehdi
M
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. mnajar@ulb.ac.be
Raicevic
Gordana
G
Boufker
Hicham Id
HI
Fayyad Kazan
Hussein
H
De Bruyn
Cécile
C
Meuleman
Nathalie
N
Bron
Dominique
D
Toungouz
Michel
M
Lagneaux
Laurence
L
D000273:Adipose Tissue / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D001853:Bone Marrow / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014470:Umbilical Cord / Q000473:pathology*
D015703:Antigens, CD; D015232:Dinoprostone; D007213:Indomethacin