title: Mesenchymal stem cells efficiently inhibit the proinflammatory properties of 6-sulfo LacNAc dendritic cells.
abstract: 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.
authors: Institute of Immunology, Medical Faculty, Technical University, Dresden, Germany.
authors: Rebekka
authors: R
authors: Wehner
authors: Diana
authors: D
authors: Wehrum
authors: Martin
authors: M
authors: Bornhäuser
authors: Senming
authors: S
authors: Zhao
authors: Knut
authors: K
authors: Schäkel
authors: Michael P
authors: MP
authors: Bachmann
authors: Uwe
authors: U
authors: Platzbecker
authors: Gerhard
authors: G
authors: Ehninger
authors: E Peter
authors: EP
authors: Rieber
authors: Marc
authors: M
authors: Schmitz
mesh_terms: 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
chemical_list: 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