Mesenchymal stem cells efficiently inhibit the proinflammatory properties of 6-sulfo LacNAc dendritic cells.
Mesenchymal stem cells emerged as a promising treatment modality for steroid-refractory graft-versus-host disease, which represents a major complication of allogeneic hematopoietic stem cell transplantation. Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses and play a crucial role in the pathogenesis of graft-versus-host disease. Here, we investigated the impact of mesenchymal stem cells on the proinflammatory capacity of 6-sulfo LacNAc (slan) dendritic cells, representing a major subpopulation of human blood dendritic cells. Mesenchymal stem cells markedly impair maturation of slanDCs and their ability to secrete proinflammatory cytokines, which was dependent on prostaglandin E(2). In contrast, the release of anti-inflammatory IL-10 was improved by mesenchymal stem cells. Furthermore, mesenchymal stem cells efficiently inhibit slanDC-induced proliferation of CD4(+) and CD8(+) T cells and polarization of naïve CD4(+) T lymphocytes into Th1 cells. These results indicate that mesenchymal stem cells significantly impair the high proinflammatory capacity of slanDCs and further substantiate their potential for the treatment of graft-versus-host disease.
Wehner
Rebekka
R
Institute of Immunology, Medical Faculty, Technical University, Dresden, Germany.
Wehrum
Diana
D
Bornhäuser
Martin
M
Zhao
Senming
S
Schäkel
Knut
K
Bachmann
Michael P
MP
Platzbecker
Uwe
U
Ehninger
Gerhard
G
Rieber
E Peter
EP
Schmitz
Marc
M
D000606:Amino Sugars / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D000097802:CD83 Antigen
D000606:Amino Sugars; D015703:Antigens, CD; D051940:B7-2 Antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C467438:6-sulfo-LacNac